Indian Patents. 211734:BENZOTHIAZOLE DERIVATIVES

Title of Invention	BENZOTHIAZOLE DERIVATIVES
Abstract	This invention related to novel benzothiazole derivatives of the formula wherein the substituents are as described in the specification.

Full Text	To a solution of 2-chloro-4-methoxy-7-phenjd-benzothiazole (150 mg, 0.54 mmol), in dioxane (5 ml) was added 3-(aminomethyl) -pyridine (176 mg, 1.6 mmol) and mis mixture was stirred at 100 °C for 18 h.. The solvent was then evaporated and the mixture taken up in methanol (8 ml) and ultrasonnicated for 10 min. to precipitate the product, which was washed with methanol (5 ml), and dried under vacuum (0.05 mmHg, 60 °C) to afford the title compound as a white solid (58 mg, 31 % yield), MS: m/e=348.3 (M+rf). Following ike general method of example 174, the compounds of examples 175 to 184 were prepared Example 175 f4-Memoxy-7-phenyI-benzotbia741-2-yIVpyrid4-4y1m4hyl-aniine Using 4-(aminomethyl)-pyridine the title compound was obtained as a pale yellow solid (17 % yield), MS: m/e=343.3 (M+rT). Example 176 f4-Methoxv-7-phenvl-ben2Pl4azol-2-yl)-pyridin-2-y]rnethy1-arninp Using 2-(aminomethyl)-pyridine the title compound was obtained as a white solid (32 % yield), MS: m/e=343.3 (M+H). Example 177 Ben24-(4-memoxv-7-phenvJ-hf4zothiazol-2-YlVamine Using benzylamine the tide compound was obtained as a white solid (54 % yield), MS: m/e=347.3 (M+H1"). Example 178 (2-Methoxy-ethvl W4-metiioxv-7-phenvi-benzothiazol-2--vl 1-amin >» Using 2-memoxy-ethylainrne the title compound was obtained as a white solid (56 % yield), MS: m/e=315.3 (M+H). Example 179 Cvdopropv4Tri«!4hyl-l"4-methoYv-7-phenvl-b4"7nt>iia7ii1-2-vl"l-ammp Using ammomethyl-cydopropane the title compound was obtained as a white solid (68 % yield), MS: m/e=311.2 (M+H+). Example 180 f4-Methoxy-7-phenyl-benzomiazol-2-yl)-(2-pyrio44 r {12} Using 3-(2-aminoethyl)-pyridine die crude product was obtained which was converted to its hydrochloride salt with excess 5N HCI/EtOH (2.5 eq.) and then purified by reversed phase preparative HPLC using a C18 ODS-AQ column, with a water (0.1% TFA) /acetonitrile gradient After pooling the product fractions and evaporation of solvents the i title compound was obtained as a white foam (59 % yield), MS: m/e=362.2 (M+H), Example 181 N-f4-Memoxv-7-phenyl-penzotriiazol-2-vIV4 TryHrni-hloridg salt (1:2) Using 2-(dimethylammo)-emyiamine the crude product was obtained which was converted to its hydrochloride salt with excess 5N HCI/EtOH (2.5 eq.) and then purified by reversed phase preparative HPLC, using a C18 ODS-AQ column, with a water (0.1% TFA) /acetonitrile gradient. After pooling the product fractions and evaporation of solvents the title compound was obtained as awhite foam (80 % yield), MS: m/e=3283 (M+H). Example 182 ■ f4Methoxv4-phen4-beiizothjazQl-4-yl)-44 salt (1:2) Using 4-{2-aminoethyl)morpholine the crude product was obtained which was converted to its hydrochloride salt with excess 5N HCI/EtOH (2.5 eq.) and then purified by reversed phase preparative HPLC, using a C18 ODS-AQ column, with a water (0.1% TFA) /acetonitrile gradient. After pooling the product fractions and evaporation of solvents the title compound was obtained as a white foam (67 % yield), MS: m/e=370-3 (M+H). Example 183 f4-Methoxy-7-phenvI-bgnTfttliiq4l-2-yl)-f2-piperidm--l-vi-ethvlVaminehvdr(v:hTnride salt f 131 Using l-(2-aromoethyl)-prperidine the crude product was obtained which was converted to its hydrochloride salt with excess 5N HG/EtOH (2.5 eq.) and then purified by reversed phase preparative HPLC, using a CI 8 ODS-AQ column, with a water (0.1% TFA) /acetonitrile gradient After pooling the product fractions and evaporation of solvents the title compound was obtained as a white foam (57 % yield), MS: m/e=368.2 (M+H). Example 184 2-(4-Memoxv-7-phenvI-benzothiazol-2-yIamino)-ethanol hydrochloride salt f 1:1) Using ethanolarnine the crude product was obtained which was converted to its hydrochloride salt with excess 5N HCl/EtOH (2.5 eq.) and then purified by reversed phase preparative HPLC, using a C18 ODS-AQ column, with a water (0.1% TFA) /acetonitrile gradient After pooling the product fractions arid evaporation of solvents the title compound was obtained as a white foam (60 % yield), MS: m/e=300.4 (M-s-H). Example 185 [4-Memoxy-7-f2-memyl:pyridm-4-vD-benzotM arid methyl ester The title compound is sysnthesised from (7-iodo-4-methoxy-benzothiazol-2-yl)- Example 186 (4-Menioxy-7-morpbnlin-4-y1-bm7otHazoI-2-vl)-carbamic acid methvl ester Carbamate formation using the same procedure as for (4-methoxy-benzothiazol-2-yl)-carbamic acid methyl ester yields the product as off-white solid in 58% yield. MS: m/e= 324 (M+H1"). Example 187 f4-Memoxy-7-phenvl-benzothia;4l-2-vl)-cafbamic acid benzyl ester To a stirred solution of 2-ammo4methoxy-7-phenyl-berizothia2ole (512 nig, 2 mmol) in pyridine at 90 °C was added benzyl chlorofonnate (33 ml, 23.4 mmol) in three portions over 6 hours. The reaction mixture was then evaporated to dryness and partioned between CH2CI2 (50 ml) and saturated aqueous NaQ solution (50 ml), the aqueous phase was separated and extracted further with CH2C12 (2x 50 ml) and the combined organic phases dried, fiTtered and evaporated. The crude residue was then chromatographed over SiG2 (Merck 230-400 mesh) eluting with CHaCl4tOAc (4:1) to afford the title compound as a white foam (620 mg, 79 % yield), MS: m/e=391.2 (M+H). Example 188 (4-MemoxY-7-vmyi-beiizotluazoI-2-yl)-carbamic acid methyl ester a) f 7-Iodo-4-methoxy-benzotbiazol-2-yl)-carhaiTiic acid methyl ester (4-Memoxy-benzothiazol-2-yl)-carbamic acid methyl ester (31.0 g, 130 mmol) and sodium acetate (32.3 g, 394 mmol) are dissolved in 400 ml of glacial acetic acid and slowly treated with iodine monochloride (13.5 ml, 264 mmol) at 0 °C. The reaction mixture is then slowly warmed to room temperature and stirred for 15 hours. After addition of water (1.31), the formed precipitate is filtered off and washed with water. The filter cake is then dissolved in a minimal amount of tetrahydrofurane (about 150 ml) and decolorized with 1M aqueous sodium thiosulfate. The product is precipitated by the addition of water (about 2.01), filtered off and dried at 60 °C for 12 hours. 42.3 g (89 %) white solid. MS: m/e= 364 (M). b) (4-Memoxy-7-vinvI-benzothiazol-2-vl"l-carbamic acid methyl ester (7-Iodo-4~memoxp-benzothiazol-2-yl)-carbamic acid ester (1 part), vmyltributylstannane (1.0 equivalents) andietrakis-(triphenylphosphme)-paflacHum(0) (0.1 equivalents) are combined in dioxaiie (25 parts) containing 2M Na2C03 (4.0 equivalents) and heated to reflux for 24 hours. The reaction mixture was evaporated, washed with brine and dried over MgSO. After evaporation to dryness the product was isolated by flash chromatography (silica, eluent ethyl acetate/hexanes) as a white solid (60 %). F.p.: 138-139° C. Example 189 4-Fluoro-N-f 4-methoxy-7-vinyl-benzothiazol-2-vl) -hepramide al 4-Memoxy-7-vmvl-benzothiazoi-2-ylamine (4-Memoxy-7-vmyl-berizolhiazol-2-yl)-carbamic acid methyi ester was dissolved in ethvlenglycol/2N KOH (2:1) and stirred at 100 °C for 3 hrs. Then water was added and the mixture was extracted with CH2Q2, the organic phase was washed with brine and dried over MgSO. After evaporation the residue was crystallized from CH2CI2. White crystals (64%); F.p.: 155-159 °C. b) 4-Huoro-N-f4-methosy--7--vinvl-benzothiazol-2-vI")--bpn7.3miHp Following the general method of example 1 the title compound was obtained from 4-memoxy-7-vmyl-benzothiazol-2-ylamine and 4-fiuoro-benzoic acid chloride as a white solid (85 %); F.p.: 198-199° C Example 190 f4-Methoxy-7-propenYl-benzothiazol-2-yl")-carbarnic acid methyl ester Following the general method 188b) the title compound was obtained from (7-iodo-4-methoxy-benzothiazol-2-yl)-carbamic acid methyl ester and tributyl-propenyl-stannane as a yellowish solid (75 %); F.p.: 153-156 °C. Example 191 N-f7-Ethyl4-methoxy-berizolhia2ol-2-yi1--4-fluoro-benzamide 100 mg of 4-fiuoro-N-(4-methoxy-7-vmyl-benzothiazol--2-yi)-benzamide (0.3 ramol) were dissolved in methanol (100 ml) and Pd/C (4 mg) were added. The reaction mixture was hydrogenated for 2 hrs. After filtering and evaporation of the solvent the crude product was subjected to column chromatography (silica gel, eluent MeQH/CHjCk 1:9). The title compound was obtained in form of white crystals (79 %); F.p.: 165-167° C. Example 192 (7-Acetvl-4-methoxy7benzpthiazol-2-yl)-carbamic acid methyl ester According to the method described for example 188b) the title compound was obtained from (7-iodo-4-memoxy-benzothiazol-2-yl)-carbamic acid methyl ester (1 equivalent) and (l-ethoxy-vinyl)-tributylstannane (1 equivalent) as a white solid (34 %); P.p.: 238-240 °C. Example 193 Rac-f7-(l-Hvdroxv-ethyl)-4"methoxy-benzotbia2ol-2--yl1-carbamir acid methyl ester 0.05 g of (7-acetyl-4-memoxy-benzothiazoI-2-yi)-carbamic acid methyl ester (0.00018 Mol) were dissolved in ethanol (30 ml) and 0.028 g of NaBFL, (0.00072 Mol) were added. After stirring at 40 °C for 24 hrs. the reaction mixture was diluted with water, extracted with CHaCb, the organic phase washed with brine and dried over MgSC>4. After chromatography on silicagel with CHaCk/MeOH 97:3 the title compound was obtained as a white solid (38 %); F.p.: 179 °C (dec). Example 194 (intermediate) Rac-f 7-f2-Bromo-I-hydroxy-emvl)4memQxy-ben2othiazol-2-yi1-carbamic add methvi ester 1.5 g of (4-methoxy-7-vinyl-benzomiazol-2-yl)-carbamic add methyl ester (0.0057 Mol), dissolved in THF (60 ml) were treated with H20 (6 ml) and 1.0 g of NBS (0.006 Mol) at room temperature for 15 min. Then the solvent was removed, the residue taken up in H2O (30 ml) and extracted four times with ethyl acetate (50 ml). The combined organic phases were washed with brine and dried over MgSCV After evaporation the crude product was subjected to column chromatography (sihcagel, ethyl acetate). The title compound was obtained as a white solid (78 %)> F.p.: 150-155 °C. Example 195 (intermediate) f7-(2-Bromo-l-hvdroxy-propyl)-4-memoxy-ben20tm4ol-2-yll-carbainic add methyl ester According to the method described for the example above the title compound was obtained from (4-memoxy-7-propenyl-ben2othiazol-2-yl)-carbamic add methyl ester as a foam and carried on to the next step without further purification and characterization. Example 196 (intermediate) (7-Bromoacetyl4-memoxy-benzotHa2ol-2 1.6 g of rac-[7-(2-bromo-l-hydroxy-emyl)-4-meliioxy-benzothiazol-2-yl]-carbamic acid methyl ester (0.0044 Mol) were dissolved in CHCU (100 ml) and treated with 3.8 g of MnOj (0.044 Mol) for 3 hxs. at 70 °C. The hot reaction mixture was filtered and subsequently concentrated. The crude product was crystallized from Et20 to yield the title compound as a beige solid (73 %); F.p.: 250-260 °C (dec). Example 197 (intermediate) [7-(2-Bromo-propionyl)-4-methoxy-bsnzotbia7ol-2-yH-carbainic add methyl ester 5.0 g of [7-(2-bromo-l-hydrc«y-propyl)-4-memoxy-benzothiazol-2-yl]-carbamic add methvi ester 0.0133 Mol) were suspended in water (30 ml) and 2.0 g of Cr03 (0.02 Mol), dissob/ed in acetic add (30 ml), were added. The reaction mixture was heated to 70 °C for 2 hrs. and then evaporated to dryness. The residue was taken up in sat NaHC03 (200 ml), extracted 4x with ethyl acetate (200 ml each) and the combined organic phases were dried over MgS04. The title compound was obtained as orange crystals (74 %); P.p.: 199-201 °C Example 198 (4-Methoxy-7-thiophen-2-yI-benzothiazol-2-vI"l-cariiaTm"r acid methyl ester Following the method described for (4-methoxy-7-vmyl-benzothiazol-2-yl)-carbamic acid methyl ester (Example 188b) the title compound was obtained from (7-iodo-4-methoxy-benzothiazol-2-yI)-carbamic acid methyl ester and 2-tributylstannyl-thiophen as a yellowish solid (41 %); 160-165 °C Example 199 [4-Methoxy-7-(5-memyl-thiophen-2-Yl)-benzo1hiazol-2--yll-carharnir. acid methyl ester Following the method described for (4-memoxy-7-vmyI-benzothiazol-2-yO-carbarnic acid methyl ester (Example 188b) the title compound was obtained from (7-iodo-4-methoxy-benzothia2ol-2-yl)-carbarnic acid methyl ester and 2-tributylstannyl-5-methylthiophen as a yellowish solid (40 %); 267-274 °C (dec). Example 200 r4-Methoxy-7-(2-memyl-miazol-4-Yl)-ben2othiazol-2-yl")-caTbarnic acid methyl ester 1.3 g of (7-bromoacetyl-4-memoxy-benzothiazol-2-yl)--carbamic acid methyl ester (0.0036 Mol) and 0.27 g of thioacetamide (0.0036 Mol) were dissolved in dioxane (30 ml) and stirred for 4 hrs. at 70 °C. After evaporation of half of the solvent water (40 ml) was added and the pH adjust to 7 with sat. NaHC03. A solid precipitated, which was isolated and then subjected to column chromatography on silicagel using ethyl acetate as eluent. The title product was isolated as an off-white solid (27 %); P.p.: 186-188 °C. Example 201 {4-Memoxy-7-f2-f6-memyl-p™dm-3-v4-thia7ni-4-yl\|-be methyl ester According to the method described above the title compound was obtained from (7-bromoacetyI-4-memoxy-ben20thiazol-2-yI)-carbamic acid methyl ester and 2-meliiylpyridine-5-thiocaboxamide as a yellowish solid (73 %); F.p.: 240-242 °C. Example 202 [4-Metfaosy-7-f2-pyriHiTi-?.-4-tfaiazol44Vbenzothia2ol-2-vl1-carbamic acid methvi ester According to the method described above the title compound was obtained from (7-bromoacet44methoxy-benzotbiazol-2-yl)-carbaniic acid methyl ester and pyridine-2-thiocaboxamide as a dark red solid (63 %); F.p.: 207 °C. Example 203 {7-[2-(tert-ButoxvcarbonYlammo-methyiVtHa carbamic acid methyl ester According to the method described above the tide compound was obtained from (7-bromoacetyi-4-memoxy-benzothiazol-2-yi)-carbarnic acid methyl ester and thiocarbamoylmethyl-carbaniic acid tert-butyl ester as a white solid (26 %); MS (ISP): m/e = 451 (M+rT). Example 204 f7-f2-Aroinomethvl-thiazol4vi)-4-methoxy-benzotfaiazol-2-vl1-carhamiradd ester hydrochloride f 1:11 0.075 g of {7-l2-(tert-butoxycarbonylainmo-memyl)-lhiazol-4-yl]-4-methosy-benzothiazol-2-yl}-cajbarnic add methyl ester (0.00017 Mol) were stirred in 2 ml of 2.5 M HCl/MeOH for 4 hrs. Upon cooling to room temperature a predpitate formed, which was filtered off, washed with hexane and dried. The title compound was obtained as a white solid (70 96), F.p.: 220-230 °G Example 205 r7-(2-Dirnetriylaminomrfhvl-tmazol-4-yl)4m methyl ester According to the method described for l4-methoxy-7-(2-methyl-thiazol-4~yl)-benzothiazol-2-yl]-carbamic add methyl ester the title compound was obtained from (7-bromoacetyl-4-niedioxy-benzotHa2ol-2-yl)-carbamic add methyl ester and dimethylajnino-thioacetamide as an off-white solid (11 %); F.p.: 185-189 °C (dec). Example 206 \ 7-f23-DimethyI-thiar4I-4"Vl1-4-pri4Hoxv-benzothiazol-2-ylI-carbaniLc add methyi ester According to the method described above the title compound was obtained from [7-(2-bromo-propiony!)-4-methosy-benzotbiazol-2->d]-carbamic acid methyi ester and thioacetaraide as an off-white solid (42 %); F.p.: 180-181 °C (dec). Example 207 f4-MemoxV-7-[2-flritv1-3TriinoVtiiiazoI-4-yll-ben?othiazol-2-,yli-carharnit: acid methyl ester According to the method described above the title compound was obtained from [7-(2-bromo-acety!)-4-methoxy-benzothiazol-2--yi] -carbamic acid metihyl ester and trityl-tbiourea as an off-white solid (53 %); F.p.: 135-140 °C. Example 208 [7-(2-Ami44tbia7ol4yl)4-methoxy-hen7.nthia7nl-2-y1\|-r4rbaTriic acid methyl ester 0.070 g of {4-memoxy-7-[2-(trityl-ammo)-tbia7x>l-4 add methyl ester (0.00012 Mol) were heated to reflux in 2 ml of 2.5 M HCl/MeOH for 4 hrs. After cooling to room temperature the pH was adjusted to 7 upon drop wise addition of sat. NaHCC>3. A predpitate formed, which was filtered off, washed with ethyl acetate and dried. The title compound was obtained as a white solid (23 %), F.p.: 293-296 °C (dec.). Example 209 [7-(2-T4TTi4hy1amino-tiuazol4yI)-4-methoxy-bep7-nthia741-2-vll-carbaniif: acid methvl ester According to the method described above the title compound was obtained from [7-(2-bromo-acetyl)-4-methoxy-benzothiazol-2-yl]-carbamic acid methyl ester, NN-dimethyl-thiourea and triethyiamin as an off-white solid (86 %); F.p.: 185-195 °C. Example 210 [4-Memoxy-7-f2-pyrrolidin-l-yl-thiazol-4-yl)-ben7xtthia2ol-2-yll-carbamic add methyl ester According to the method described for the example described above tie title compound was obtained from [7-(2-bromo-acetyl)-4-metnoxy-benzothiazol-2-yl]-carbarnic add methyl ester and 1-pynoUdine-carbothioamide as an off-white solid (16 %); F.p.: 199 °C. Example 211 [4-Methoyy~7-f2-piperidiqrl-yl-tfaiazol4yl)-beri2othiazol-2-vl1-carbamic acid methyl ester According to the method described above the title compound was obtained from [7-(2-bromo-acetyi)-4-methoxy-ben2othiazoI-2-yl] -carbamic acid methyl ester and 1-piperidine-carbothioamide as an off-white solid (71 %); F-p.: 209 211 °C. Example 212 [4-Methoxy-7-(2-morphoh4-4-yl-tbjazol4Yl)-benM acid methyl ester According to the method described above die title compound was obtained from [7-(2-bromo-acetyi)-4-methoxy-benzothiazol-2-yi]-carbamic acid methyl ester and 1-morphohne-carbotbioamide as a yellowish solid (41 %); MS (ISP): m/e = 407 (M+H). Example 213 J4-Memoxy-7-f2-(4-memyl-pipera2mTl-yl)-thiazol4 acid methyl ester According to the method described above the title compound was obtained from [7-(2-bromo-acetyl) 4methoxy-benzotmazol-2-yi] -carbamic acid methyl ester and 4-methyi-l -piperazmethiocarboxamide as a brownwish solid (41 %); F.p.: 143 °C Example 214 [7- (2-tert-Butoxycarbonylarnino-1 H-irni64zol-4-yl)-4-meihoxy-berizothiazoi-2-vll -carbamic acid methyl ester 0.25 g of (7-bromoacetyl-4-memoxy-benzothiazol-2-yi)--carbamic acid methyl ester (0-0007 Mol) and 0.33 g of tert-butoxycarbonylguanidine (0.0021 Mol) were heated to reflux in acetonitril (3 ml) for 3 hrs. After evaporation of the solvent the residue was triturated with water (10 ml) and filtered. The filtrate was evaporated and the residue subjected to column chromatography (siUcagel, ethyl-acetate/hexanes 1:1) to yield the title compound as a white solid (17 %); F.pj 255-265 °C. Example 215 r7-f2-Airnino-lH-iiiudazol-4-yl)4methoxy-benzodMazol-2-Yl]-carhaniic acid methyl ester 0.04 g of [7-(2-tert-butoxycarbonylairimo-lH-imidazol-4-yO yl]-carbamic acid methyl ester (0.0001 Mol) were heated to 60 °C in HO/MeOH (2.5 M, 2 ml). After evaporation of the solvent the residue was dissolved in water (5 ml) and the pH was adjusted to 8 with sat NaHCOj. The water was evaporated and the residue triturated in ethyl acetate where a precipitation formed. This was isolated and dried to yield the title compound as a grey solid (16 %); F.p.: 225-235 °C. The following examples were prepared according to the general method described for 4-methoxy-7-vmyI-benzolhiazol-2-yl-amine (Example 189a) from the corresponding carbamic acid methyl ester. 4-Memoyy-7-("2-morpTi9lin-4-vl-thiazol-4-vlVbeiizotruazol-2-yi-araine Obtained as a white solid (73 %); F.p.: 289-292 °C. 4-Mefao:re-7-[2-(4-me&vl-piperarin-1-vl)-thiazol4 Obtained as a light yellow solid (81 %); F.p.: 176 °C (dec). 4-Methoxy-7- \2- (6-memyl-pyridin-3-vl)-thiazol-4-yl1 -bpn7Qthiazol~2-yl-amine Obtained as an off-white solid (94 %); MS (ISP): m/e - 355 (M+FF). 7-f7--Airiino-ihiazol-4-vl)-4-memoxy-benzothia2ol-2-yl-amine Obtained as a white solid (56 %); MS (ISP): m/e = 279 (M+FT). 7-f2-Dimemylarnino-thiazol-4-yl)-4-memoxy-ben2othia2ol-2-yi-arnm Obtained as a beige solid (62 %); F.p.: 225-238 °C. 4-Methoyy-7-miophen-2-4-benzothiazol-2-y]-aimne Obtained as a light brown solid (85 %); F.p.: 215-219 °C. 4-Metfaory-7-f2-pyridm-2-vi-ftta7rii-4-yl)-berizomiagol-2-vi-aniine Obtained as a light yettow soEd (67%); F.p.: 302 "C (dec). 4-Metfaox7-7-f2-pyiToHdin-1-y4-iiiia2ol4yiVben2otlna7.n1-?.-v1-arnirifi Obtained as a light brown solid (99 %); P.p.: 270 °C (dec). 4-Metfaoyy-7-f2-piperidin-1-4-thiazol4ylVbenzofliiay.nl-9.-Yi-amiTip Obtained as a light brown solid (75 %); MS (ISP): m/e = 347 (M+PT). 4-Methox>r-7-f2i-metfa4-thi37n]4yi)-benzothia4ol-2-Td-4mine Obtained as an off-white solid (81 %); P.p.: 262-265 °C. 4-Methoxy-7r (5-roethvi-thinphen-2-yl)-benzothia7-oI-?-yl -aminp Obtained as an off-white solid (81 %); F.p.: 195-205 °C (dec). 7-(2,5-PiT"4>"y4-th4a7i41U-444-melhoxv-berlzo1hiazol-2-1\|d-amine Obtained as a yellow solid (5 %); P.p.: 201-20 3 °C. FoUowing the general method of example 1 the fallowing examples were obtained from corresponding benzothiazol-2-yl-amines and 4-fluoro-benzoic add chloride: Example 216 4-Huoro-N-U-methoxy-7-f2-morpholm-4-vl-lbJazoI-44vlVbenzothia2ol-2-vl1-benzaTTiidg Obtained as an off-white solid (53 %); P.p.: 225-227 °C. Example 217 N-r7-f2-Ammo-tiuazol-44y1)-4-me&oxy-ben Obtained as a white solid (85 %); F.p.: 262-264 °C. Example 218 4-F]uoro-N-f4-melho3re-Xf9-f6-meth)fl-pp4T4 benzamide Obtained as an off-white solid (79 %); MS (ISP): m/e = 477 (M+fT). example zi? N-{7-(2-Dim4iiYlamipo-thiazol-4-Yl)-4-metbj:iC4 Obtained as a light yellow solid (29 %); P.p.: 218-220 °C Example 220 4-Fluoro-N-f4-metboxy-7-tMophem-2-yl-benzotfaia2oI--2-ylVbenzainide Obtained as a light yellow solid (72 %}; P.p.: 242-250°C. Example 221 4-Fluoro-N-l4-methoxy-7- \2-( 4-methyI-piperazin- l-yl)-thiazol-4-yl\| -benzothiazoI-2-yll- benzamide Obtained as an off-white solid (66 %); F.p.: 138 "C (dec). Example 222 4-Huoro-N-r4-metb.oxy4-7-(2-pyridin-2-4-diiazol-4-ylVben2otlu4tzol-2-yl1-benz3TTiiH4 Obtained as an off-white solid (92 %); F.p.: 150 °C (dec). Example 223 4-Fluoro-N- r4-methoxy-7-(2-pyrrolidin- l-yl-thia2ol-4-yl)-benzothiazol-2-yI1 -Ivnra mid* Obtained as an off-white solid (82 %); MS (ISP): m/e = 455 (M+H). Example 224 4-Fluoro-N- f 4-methoxy-7-f 2-methyl-tbiazol-4-yl)-benzothiazol--2-"id1 -benzamide Obtained as a white solid (36 %); F.p.: 217-219 °C. Example 225 4-Wnoro-N-f4-methoxv-7-("5-melhyI-thiophen-2-4)-hf4n74thiazol--2-yll--benzamide Obtained as an off-white solid (70 %); P.p.: 192-196 °C (dec). Example 226 N-f7-(2,5-Dimethyl-lfaiazol-4-yl)-4-memory-Hgn4 Obtained as an off-white solid (42 %); F.p.: 205-206 °C (dec.). Example 227 4-ChloromethvI-N44-methoxy-7-f2-morpholin-44 benzamide 0.165 g of 4-methoxy-7-(2-morpholm-4-yi-thiazd4-yl)-benzothiazol-2-)4aniine (0.00047 Mol) were dissolved in dioxane (5 ml) and combined with. 0.1 nil of triethyiamine (0.0007 Mol), 0.006 g DMAP (0.000047 Mol) afcd a solution of 0.116 g of 4-(chlormethyl)benzoylcblorid (0.00062 Mol) in dioxane (1 ml). The reaction mixture was stirred for 6 hrs. at 70° C. After cooling down to room temperature, water (10 ml) and sat. NaHCC>3 (10 ml) were added. A precipitation formed. It was filtered, washed with water and tried. This crude product was subjected to column chromatography (sOicagel, CH2Cl2/MeOH 19:1). The tide compound was obtained as a light yellow solid (65 %); F.p.: 166-168 °C. The following examples were prepared from the corresponding 7- substituted 4-meihoxy~ ber4thiazol-2-yl-amirie$ according to the above described method: Example 228 4-Chloromethyi-K- J4-methoxy-7-f 2-f 6-methvl-pyricUn-3-ylVtbJazol-4-iAl -benzotbiazol-2-yi}-ben7.amide Obtained as an off-white solid (68 %); F.p.: 230-250 °C. Example 229 4-Cbloromethvl-N-{4-methoxy-7- [2- (trit4-ammo)-tbia2ol4yll-beiizothiazol-2-Yl\-benzamide Obtained as a white solid (42 %); F.p.: 163 °C (dec.). Example 230 44Chloromethvl-N-r7-f2-Himrthylamin4-t4 bemsBHu? Obtained as a light yellow solid (36 %); F.p.: 183-186 °C. Example 231 4-CMorome&yl-N-f4-me&oxy-7-lHophen-2-4-bei4othiazol-2-ylVbenzaroide Obtained as a light yellow solid (60 %); F.p.: 183-209 °C (dec). Example 232 4-Chloromethyl-N-f4-methoxy-7-(?.-pvridin-2-yl-thia4 henTamide Obtained as a light brown solid (79 %); F.p.: 195-201 °C. Example 233 4-Chloromethyl-N- f 4-methoxy- 7- f 2-methyl-thiazol-4-yl"l-berizothiazol-2-yl1 -benzamide Obtained as a white solid (72 %); F.p.: 140-145 °C. Example 234 4-ClrioromethYl-N-f4-roethoxy-7-f5-methvl-i4 benzamide Obtained as a yellow solid (93 %); F.p.: 130-146 °C. Example 235 4-U(2-Methoxv-ethylVmelhyl-aminn]-methyl4N-f4-memoxy-7-(2-morpholni-4-yi-th iazol-4-yl Vbenzothia2ol-2-y11 -b»r>Tami H e. 0.035 g N-(2-methoxyethyl)-methylamine (0.00039 Mol) and 0.064 g (4-chloromemyl-N- [4-methoxy-7-(2-moipholm-44yl-tMazol4y4 Mol) dissolved in THF (2 ml) were heated to reflux for 4 hrs. After cooling to room temperature and evaporation of the solvent the residue was triturated with water (7 ml). A precipitation formed, which was filtered, washed with water and dried yielding the title product as an off-white solid (79 %); F.p.: 100-110 "C. The following examples were prepared according to the method above from N-(2-methoxy-benzothiazol-2-yl] -benzamides: Example 236 4-Jf(2-MethoYy-em7l)-memyI-ammoUmethvl}-N-f4-m thiazol-4-yll -benzothia2ol-2-yn-benzamide Obtained as a white solid (79 %); F.p.: 119-128 °C Example 237 N-[7-f?.-Aminn-itoazol4yl)4methoxv-benzothiazol-2-414-fff2-memoxy-ethyD-methyl-aminol -methyl] -benzamide 0.1 g of 4-{[(2-melhox7-e&yl)-methyl-arnmo]-methyl}-N-{4-memoxy-7-[2-(trit7l-ammo)-tinazol-4-yl]-benzothiazol-2-yi}-benzainide (0.00014 Mol) were treated with cc HC1 (0.03 ml) in MeOH (1 ml) for 1 h at reflux. After evaporation of the solvent the residue was taken up in water (10 ml), treated with sat NaHCOs (10 ml) and extracted 4x with ethyl acetate. The combined organic phases were dried over Na2SO Example 238 44ff2-Memo:re-emyiymemvl-aTTiinf»1-m44 vO-thiazol-4-Yn -benzothiarol-2-yIl-benzamide Obtained as a light yellow foam (69 %); MS (ISP): m/e = 560 (M+FT). Example 239 N47-f2-Dimethvlainmo-tbiazol4yl)-4-memox4 ethvD-methvi-aminol -methvU-benzamide Obtained as a light yellow solid (47 %); F.p.: 85-95 °C. Example 240 4-lk2-Metfaoxy-elhyI)-memvI-annno1-methyll-N-(4-methoxy-7-thiophen-2-vl-i benTnfhiazoI-2-yn-benzamide Obtained as a light beige solid (44 %); F.p.: 58-78 °C. Example 241 4-W2-Memortr-ethvi)-methvi-ammolmediTi4N-f4-m 4-yi )-benzothia2ol-2-yfl -benzamide Obtained as a light yellow solid (54 %); MS (ISP): m/e = 546 (M+rT). Example 242 4-nf2-Methoxy-ethviVmethvl-animo1-methvll-4 benzothia2ol-2-yil -benzamide Obtained as a white solid (36 %); F.p.: 140-145 °C. Example 243 4-4f2-Methoxv-eth4Vmeth4-aminn]-melh4}-N-f4-methomr-7-f5-meth4thiophen-2-yi) -benzothiazol-2-vn -benzamide Obtained as alight beige solid (73 %); F.p.: 83-90 °C. Example 244 N- f 4-Methoxy-7-f2-morpholin-4-yi-thi4nI-4-4)-benzotmazo?-2-Yl]-4-pTTrolidin- 1-vi-methyl-benzamide 0.032 g pyrrolidine (0.00045 Mol) and 0.075 g (4-chloromethyl-N-[4-methQ35y-7-(2-mo4holm-4-yl-1hia2ol-4-yl)-beiizoiiiiazol-2--yl]--benzamide (0.00015 Mol) dissolved in THF (2 ml) were heated to reflux for 1 h. After cooling to room temperature and evaporation of the solvent the residue was triturated with water (7 ml). A precipitation 1 formed, which was filtered, washed with water and dried yielding the title product as an off-white solid (87 %); F.p.: 120-130 °C The following examples were prepared aeeoording to the method above from pyrrolidine and the corresponding 7- substituted 4-&bromelhyl-N-[4-melhoxy-ben20lhiazol-2-yl]-benzamides: Example 245 N-i4-Memoxv-7- f 2-f 6-methvl-pvridin-3-vi Vthiazol-4-vl 1 -benzothiazol-2-vll-4-pvreoh"dm- 1-yi-methyl-benzamide Obtained as a light brown solid (58 %); F.p..- 230-231 °C. Example 246 N-l4-Methoxy-7-f2-flrifrri-ainmo)-thiazol-4-yl1-be methvl-benzamide Obtained as a light yellow solid (89 %); P.p.: 122-135 "C. Example 247 N- [7-f 2-A4inrwtKiqzol-4-4)-4-metlioxy-beii20tHazol-2-vl1-4-pyrrolidJn- 1-yi-methyl-hpnTamidebydrni-bloride (1:1) 0.055 g of N-{4-methoxy-7-[2-{tiit)d-ainmo)-tbiazol-4-vl]-benzotiiiazol-2-yi}-4-pyrrolidin-l-ylmetlt)i-benzamide (0.000078 Mol) were dissolved in MeOH (0.5 ml) and ccHQ (0.015 ml). After refluxmg for 1 h the solvent was evaporated, the residue treated with ethyl acetate, filtered and isolated This material was triturated in EtOH whereby crystals formed, which were washed with EtjO. After drying the title compound was obtained as a white solid (62 %); F.p.: 228-240 °C. Example 248 N-i7-f2-DJTnetHy1aTninn-tHa7X>l-4-YD-4-metfao4 methyl-benzamide Obtained as a light yellow solid (75 %); P.p.: 120-136 °C. Example 249 N-(4-Methoxv-7-thiophen-2-yl -ben7Jrthia7ol-2-yl4-4-pvrrolidin-l -vi-methyl-hemaTniHf; Obtained as a light beige solid (47 %); P.p.: 174-190 °C (dec). Example 250 N44-Methoxy"7-(2-pyridm-2-vi-tfo"azoI-4-yi)-ben2a44 methvi-benzamide Obtained as a light fellow foam (48 %); MS (ISP): m/e = 528 (M+H). Example 251 N- f 4-Methoxv-7-f 5-methvI-thiophen-24)-beii2omiazol-2-yl1 -4-rmroh4-l-yl-rnethyl- Obtained as a light beige solid (67 %); F.p.: 140-149 °C (dec). Example 252 N-f4-Melhoxv-7-(2-rneth4-tMazol4yl)-benzothiazol-2-vi1-4-pyrroHdm-l-vl-me henTamiHp Obtained as a light yellow solid (44 %); F.p.: 123-134 °C. Example 253 N-f4-Methoxy-7-tbinpbw-?-yi-benzotbia2ol-2-4)-2-meliiyi-isonicotirjamide 0.21 g of 4-methoxy-7-thiopben-2-yl-beim)tbiazol-2-yl-amine (0.0008 Mol) together with 0.27 ml triethylamine (0.002 Mol), 0.01 g of DMAP and 0.20 g isonicotinic acid chloride (0.001 Mol) were heated to reflux for 20 hrs. in dioxane (10 ml). After cooling to room temperature water (20 ml) and sat. NaHC03 (15 ml) were added. A precipitation formed, which was filtered, washed with water and dried. This crude product was subjected to column chromatography (suicagel, ethyl acetate) to yield the title compound as a yellow solid (58 %); P.p.: 203-211 °C (dec.). The following examples were prepared accoording to the method above from isonicotinic acid chloride and the corresponding 7- substituted 4-melhoxy-berizothiazol~2-yI-amines: Example 254 N- f 4-Methoxy-7-f 2-pvriHiTi-7.-4-ihia2ol-4-4Vbenzothiazol-2-yl1 -2-methyl- isonicotinamide Obtained as a light yellow solid (38 %); MS (ISP): m/e = 460 (M+H1"). Example 255 N-[4-Memoxy-7-f2-pyrToHdm-l-yl-thia2ol-4-4)-benzotluazol-2-Tdl--2-methyl-isonicotinamide Obtained as a yellow solid (9 %); P.p.: 195-215 °C. Example 256 N-(4-Memoxy-7-(2-f4-memvl-pipera2in-l-yl)-thiazo4 isonicotinamide Obtained as a yellow foam (4 %); MS (ISP): m/e = 481 (M+rT). Example 257 N- [4-Methoxy-7-f 5-Tnpthyl -thinphen-? -yiVbenzotbiazol-2-vll -2-methyi--isonicotiTiamidf" Obtained as a light orange foam (65 %); MS (ISP): m/e = 396 (M+H). Example 258 Morpholine-4-carboxyiic acid (4-methoxy-7- f2-(6-memvl-pyriHin-3-yIVthiazol-4-Yi1-benzothiazol-2-ylt -amide 0.1 g of 4-methoxy-7-[2-(6-methyl-pyridm-3-ylVthia74 (0.00028 Mol) were dissolved in dioxane (2 ml) and treated with 0.047 ml triethylamine (0.00034 Mol) and 0.164 ml of phosgene (20 % in toluene) (0.00031 Mol). After stirring for 2 his. at room temperature 0.122 ml of morpholine (0.0014 Mol) were added and the whole mixture was stirred for 16 hrs. at ambient temperature. Upon addition of water (5 ml) a precipitation formed, which was filtered, washed with water and dried. This crude material was triturated with hot MeOH and after cooling to room temperature filtered. The filtrate was evaporated and the residue subjected to column chromatography (silicagel, CH2Cl2/MeOH + 1 % NH4OH). The title compound was obtained as a light yellow solid (7 %); MS (ISP): m/e = 468 (M+H+). Example 259 Morpholine-4--carboxyiic acid [4-memoxy-7-f2-py"4iTi-2-vl--tbia7fi14-y]")-benzot>iia7.n1-9-yil -amide 0.1 gof4-metioxy-7-[2-pyricfo-2-yl}-thiazoI444 (0.00029 Mol) were dissolved in THF (5 ml) and treated with 0.063 ml ethyldiisopropylamine (0.00037 Mol), DMAP (1 mg) and 0.029 mg ©f tripbMgese (00)001 Mol). After faeatnofto reflux for 30 min., 0.0322 ml of morpholine (0.00037 Mol) and another 0.062 ml of ethyldiisopropyiamine were added and the whole mixture was stirred for 16 irxs. at reflux. After cooling to room temperature water (10 ml) was added and the reaction mixture was extracted with ethyl acetate (4x, 15 ml each). The combined organic phases were dried over Na2S04, filtered and evaporated. The residue was subjected to column chromatography (silicagel, ethyl acetate). The title compound was obtained as a light yellow solid (7 %); F.p.: 152-178° C (dec.). Example 260 Morpholine-4-carboxyiic acid [4-methoxy-7-(2-memvl-1iiiazol-4-Yl)-benzothiazol-2-yll-amide 0,07 g of 7-(2-Ammo-thiazol4yl)4memoxy-beri20thia2ol-2-yl-amine (0.00025 Mol) were suspended in dioxane (4 ml) and treated with 0.028 g of NaH (60 % dispersion in oil) (0.0006 Mol) for 1 h at room temperature. Then 0.11 ml of triemylamine (0.00076 Mol) and 0.07 ml of morpholine-4-carbonylchloride (0.0006 Mol) were added and the reaction mixture was stirred at room temperature for 3 hrs. Then water (15 ml) was added and the reaction mixture was extracted with ethyl acetate (4x, 20 ml each). The combined organic phases were dried over Na2SOfc filtered and evaporated. The residue was subjected to column chromatography (silicagel, ethyl acetate). The title compound was obtained as a light yellow solid (61 %); P.p.: 223-226 °C (dec). The following examples were prepared according to the method above from morphoIin-4-carbonylchloride and the corresponding 7- substituted 4-rnethoxy-benzothiazol-2-ylamines: Example 261 Morpholinp-A-carboxvlic acid {4-methoxy-7-f2-f4-methyl-piperariTi-l-yT)-thia7:ol-4-vn- benzotbia7.n]-2-vU-aTnide Obtained as a beige solid (40 %); F.p.: 150-170 °C. Example 262 Morphol"4-4-4Tfeoxylic acid r4-methoxy-7-f?-pippridin-1 -y1-thia7o1-4-y1)-benzothiazol-2-vil-amide Obtained as a light yellow solid (25 %); P.p.: 227-234 °C. Example 263 Morpholine-4rcarboxviic acid (4-methoxv-7-tfaiopheD-2-4-bCTT7nt4ia741-?-y?)-aTniHp Obtained as a light beige solid (37 %); F.p.: 175-182 °C (dec). Example 264 MorphoIine-4-carboxylic acid r4-metfaoxv-7-f5-metfavl-tbiophen--2--TiVben2X)thiazol-2- yj] -amide Obtained as a light beige solid (59 %); F.p.: 173-180 °C (dec). Example 265 4-Hydroxy-piperidme-l-carboxvhc acid r4-methoxv-7-(2-methvi-thiazol-4-vD-benzothia2ol-2-yH -ami dp To a suspension of 0.070 g of 4-memoxy-7-(2-memyl-tbiazol-4~yl)-benzotm"azol-2--ylamine (0.00025 Mol) in THF (4 ml) at room temperature were added 0.054 ml N-ethyl-diisopropylamine (0.00031 Mol) and 0.001 g DMAP. 0.025 g of txiphosgen (0.000085 Mol) were added and the whole mixture was heated to 70 °C for 1 hr. Then another 0.054 ml N-ethyl-diisopropylaimne (0.00031 Mol) and 0.031 g of 4-hydroxy-piperidin (0.00031 Mol) were added and the reaction mixture was stirred at 70 °C for 1.5 hrs. Upon cooling to room temperature a precipitation formed, which was filtered and washed with THF. The filtrate was evaporated and the residue was subjected to column chromatography (silicagel, CH2Gb/MeOH 9:1). The title product was obtained as a white solid (11 %); F.p.: 145-150 °C. The following example was prepared according to the above described methode from 4-methoxy-7-(5-methyl-tMophene-2-yl)-benzothiazol-2-yl"amine: Example 266 4-Hvdroxy-piperidine-l-carboxyHc acid f4-memoxy-7-(5-methvi-tbiophen-2-vD-benzothia7.n"-2-yn -amide Obtained as a yellow solid (10 %); F.p.: 197-204 °C (dec). The fallowing example was prepared according to the methode described above from N~metnyl-piperazine and 4-metkoxy-7-(2-methyl-thiazol4yl)-benzothiazal-2-ylamine: Example 267 4-Methyi-piperazine-l-carboxviic acid f 4-methoxy-7-f2-methyl-thiazol-4-Tiy benzothiazol-2-yn -amide Obtained as a white solid (8 %); F.p.: 179-181 °C. Example 268 {2-f4-(44-Me&oxy-7-morphoIin4-yi-benzodn4zoi-2-yIcarbamoyi)-plieDyi?-ediyif-metnyi-carbamic acid tert-butvl ester Using [2-(4-chlorocarbonyl-phenyl)-ethyl]-inemyl-carbamic add tert-butyl ester the title compound was prepared using the general method of example I as white solid (16 %), MS: m/e= 527 (M+rT). Example 269 N-f4-Memoxy-7-morpholin-4-yl-beiizothiazol-2-ylV4-flJ44-tetrafluoro-emoxy)- bpn7amide Using 4-(l,l,24-tetrafluoro-ethoxy)-benzoyl chloride the title compound was prepared using the general method of example 1 as light yellow solid (35%), MS: m/e= 486 (M+H). Example 270 4-ff2-Mefooxy-ethyl)-methyl-snlfamovl1-N4 2-ylVben2amide Using (2-methoxy-ethyl)-methyl-sulfamic acid chloride the title compound was prepared using the general method of example 1 as red solid (44%), MS: m/e= 521 (M+H). Example 271 N-f4-Me&oxy-7-mQTpholin-4-vl-beireotbiazol-2-ffi Using 4-(trifiuoromethyl)-benzoyl chloride the title compound was prepared using the general method of example 1 as white solid (58 %), MS: mJe= 438 (M+H). Example 272 N-f4-Me&oxy47-moiTJho1m-4r-Td-benzotlu42ol-4 Using 3-(trifluoro-methosy)-benzo)d chloride the title compound was prepared using the general method of example 1 as light yellow solid (84%), MS: m/e= 454 (M+H). Example 273 N-f4-Methoxy-7-morpholm4yl-benzotMazol-2-yl)4trifluoromemoxv-benraTtiiHft Using 4-(trifluoro-methoxy)-benzoyI chloride the title compound was prepared using the general method of example 1 as yellow solid (77 %), MS: m/e= 453 (M). Example 274 4-Em4-N-f4-memoxy-7-morpholm-4-4-benzotlnazol-2-4Vbenzainide Using 4-ethyi-benzoyl chloride the title compound was prepared using the general method of example 1 as white solid (21 %), MS: m/e= 397 (M+H). Example 275 4-Fluoro-N-(4-methoxy-7-moipholm4-vl-benzotrda2ol-2-vlVbenzamide Using 4-fluoro-benzoyl chloride the title compound was prepared using the general method of example 1 as white solid (64 %), MS: m/e= 388 (M+H). Example 276 N-(,4-Methoxy-7-morpholm4yl-beiizotHa4ol-2-ylV2-memTi-isonicotmamide Using 2-methyl-isonicotmyl chloride the title compound was prepared using the general method of example 1 as white solid (72 %), MS: m/e= 385 (M+H). Example 277 N-(4-Methoxy-7-moi4holm44-benzothiazol-2-yl)-beMamide Using benzoyl chloride the title compound was prepared using the general method of example 1 as white solid (85 %), MS: m/e= 370 (M+H1"). The following compounds are described according to the general procedure C in Example 126: Example 278 4-Chloro-3-f f ethyi-f2-metfaory-4hy? }-amJTio J -methyl ?-N-f4-mefaoxf~7-moTphn)m-4-vl~ Using 4-chloro-3-cMoromethyl-benzoyl chloride and emyl-(2-memoxy-emyl)-arnuie the title compoimd was prepared using the general procedure C as off-white solid (69 %), MS: m/e= 519 (M+H). Example 279 N-f4-Metho:4-7-morpholm4yl-hm7nthTa7dl-24 Using 3-diloromethyI-benzoyl chloride and memyiUmine the title compound was prepared using the general procedure C as white solid (44 %), MS: m/e= 413 (M+H). Example 280 4-CMoro-N-(4-memoxy-7-moi4holTn4-Yl-ben2othiazol-2-yi)-3-metDYlamin nm4-hyl - hpn Tan-ride Using 4-chloro-3-chloromethyi-benzoyi chloride and methylainine the tide compound was prepared using the general procedure C as light yellow solid (69 %), MS: m/e= 447 (M+H). Example 281 4-CrJoro-3-{ff2-methoxv-emTlVmemvl-anTinol-mem4}-N-f4-memoxy-7-morpholin-4- yi-benzothiazol-2-1dVbenzamide Using 4-chloro-3-chloromethyl-benzoyl chloride and (2-methoxy-ethyl)-methyI-amine lie title compound was prepared using die general procedure C as off-white solid (54 %), MS: m/e= 505 (M+H1"). Example 282 4-Chloro-3-f(2-memoxv-emvlarnmoVmemyl1-N-f4-methoxv-7-morpholin-4-yl- benzotbiazol-2-yI)->"pn7jimide Using 4-chloro-3-chlororaethyl-benzoyi chloride and 2~memoxy-ethylamine the title compound was prepared using die general procedure C as off-white solid (69 %), MS: m/e=491(M+H+). Example 283 4-Chloro-N- f 4-memoxy-7-moiphoIm4-yl-benzomiazoI-2-yl)-3-pvrrolidm-1 -vimethvi-henzamide Using 4-chloro-3-cbloromethyl-benzoyl chloride and pyrroKdine the title compound was prepared using the general procedure C as light yellow solid (72 %), MS: m/e= 487 (M+fT). Example 284 1 - f 4-f 4-Benzyloxy-7-morpholin-4yI-ben2othiazol-2-vl(aibamoyl)-ben7y;l1 -pyridininm- chloride Using 4-benzyloxy-7-morphoh4-4-yl-faeri2otHa2oI-2-ylamineJ 4-chlorometh.yI-benzoyl chloride and pyridine the title compound was prepared using the general procedure C as white solid (80 %), MS: m/e= 538 (M). Example 285 3-Pluoro-N-f,4-methcocy-7-moTphoh44-yl-benzothiazol-2-4)4pvn-ohdin-1 -ylmethyi- benzamide Using 4-chIoromemyi-3-fluoro-benzoyl chloride and pyrrolidine the title compound was prepared using the general procedure C as yellow solid (25 %), MS: m/e= 471 (M+H). Example 286 3-T (2-Methoxy-e&7k™4)-™fttb.yri -N-(4-metboxv-7-morpholin-4r-vl-~berantKia7.ftU2-. yl)-h»n7amiHp Using 3-chloromethyl-ben2oyl chloride and 2-methoxy-emylamine the title compound was prepared using the general procedure C as light yellow solid (68 %), MS: m/e= 457 (M+H). • Example 287 3-W2-MethoCT-emyiymemvl-aTriinol-memyi4 benzothiazol-2-yl)-4enzamide Using 3-chloromethyl-benzoyl chloride and (2-methoxy-ethyl)-methyl-airnne the title compound was prepared using the general procedure C as yellow solid (75 %), MS: m/e= 471 (M+-H). Example 288 l-r4-(4-Me&o;4-7-morpholm-4-4benzothiazoI-24 chloride Using 4-cHoromethyi-benzoyl chloride and pyridine the title compound was prepared using the general procedure C as white solid (33 %), MS: m/e= 462 (M). Example 289 N- (4-Memoxv-74morpholm-4-vl-benzothiaail-2-4"}-3-pvrroIi4in- 7 -yTmffthyj-hwigam ifo Using 3-chloromethyl-benzoyl chloride and pyrrolidine the title compound was prepared using the general procedure C as light yellow solid (65%), MS: m/e= 454 (M-t-H). Example 290 4- f (4-Emoxv-emyiaminoVraethyl ] -N-( 4-methoxy-7-morpho?Tn -4-yl-benzothiazol-2-yl)- benzamide Using 4-chloromethyI-benzoyl chloride and 2-emoxy-ethylarnine the title compound was prepared using the general procedure C as white solid (18 %), MS: m/e= 471 (M+rf"). Example 291 [R1-N-f4-Memoxy-7-morphoiin-4-yl-benzothiazol-2-yl44f3-memoxy-pyn4Hdin-l-yl- methyD-benzamide Using 4-chloromethyl-benzoyl chloride and [jRJ-S-methoxy-pyrroIidine the title compound was prepared using the general procedure C as light yellow solid (18 %), MS: m/e= 483 (M+H). Example 292 N-(4-Methoxy-7-morpholin4yi-benzothia?pl-2-yl4 Using 4-chloromethyl-ben2oyl chloride and methylamine the title compound was prepared using the general procedure C as light yellow solid (63 %), MS: m/e= 413 (M+tT). Example 293 f5l-N-(4rMe&oxy-7-morpholm-4-vl-benzothi ylmetind)-benzarnide Using 4-chloromethyl-benzoyl chloride and [S]-3-methoxy-pyrroUdine the title compound was prepared using the general procedure C as light brown solid (13 %), MS: m/e=483(M+H+). Example 294 4-Azetidm-l-ylroemyl-N-(4-metfao:xy-7-mo Using 4-chlorornethyI-benzoyl chloride and azetidine the title compound was prepared using the general procedure C as light yellow solid (33 %), MS: m/e= 439 (M+rT"). Example 295 4-fl-(2-Me&oxy-emylainmo)-etfayl1-N-(4-memo4 vl)-benzamide Using 4-( l-chloro-ethyl)-benzoyl chloride and 2-methoxy-ethylamine the title compound was prepared using the general procedure C as yellow solid (52 %), MS: m/e= 471 (M+fT). Example 296 4-n-ff2-Methoxy-emyl)-mem\d-arnmo1-etfavll-N-(4-memoxT--7-morpholm-4-4- benzothiazol-2-yll-benzamide Using 4-(l-chloro-ethyi)-beriZoyl chloride and (2-methoxy-ethyl)-methyl-arnme the title compound was prepared using the general procedure C as yellow solid (91 %), MS: m/e= 485 (M+rT). Example 297 N7(4-Memoxy-7-morphoHn4yl-ben?ptbiazol-2-yl4-4-f 1-pvrrolidin-1 -yl-ethylV benzarnide Using 4-(l-chloro-ethyl)-benzoyi chloride and pyrrolidine the title compound was prepared using the general procedure C as yellow solid (68 %), MS: m/e= 467 (M+H). Example 298 4-(2-Dimethvfeminr>ethylsulfanylmet44 benzothiazol-2-vl"l-benzamide Using 4-chloromethyl-benzoyl chloride and 2-dimemylainino-ethanethiol the title compound was prepared using the general procedure C as yellow solid (52 %)> MS: m/e= 487 (M+H). Example 299 (roc) N-f4-Me1noxy-7-morpholin-4-yl-berizotiiia2oi-2-yi)-4-(fmetn4-f4T4,4-trifluoro-3- hydroxy-huty1)-amino1-roeuiYll-beiizaniide Using 4-chloromethyi-benzoyl chloride and (roc)-1,1,1 -trifiuoro-4-methylamino-butan-2- ol the title compound was prepared using the general procedure C as white solid (89 %), MS: m/e= 539 (M+rT). Example 300 4-\|[Etfayl-f2-memoxv-emvlVaniino1-meth4l-N-f4-methoxv-7-morpholig-4-yl- benzotmazol-2-yl)-benzainide Using 4-cmoromethyl-benzoyl chloride and (2-methoxy-ethyl)-ethyl-amine the tide compound was prepared using the general procedure C as light brown solid (62 %), MS: m/e=485(M+rT). Example 301 4-4f2-Emoxy-emylVeth\4-anu4ol-memvn-K-f4"memoxv-7-morphoIin-4-4- hpn7Athia?ol-2--yl)-benzairiide Using 4-chloromethyl-benzoyl chloride and (2-ethoxy-ethyI)-ethyi-aniiiie the title compound was prepared using the general procedure C as light brown solid (66 %), MS: m/e=499(M+H). Example 302 3-Huoro4W2-meikoxy-e&ylVmethyl-airimo1-4 yl-benzothiazol-2-yl"l-ben2amide Using 3-fluoro-4-chIoromethyI-ben2oyi chloride and (2-methoxy-ethyI)-methyi-amine the title compound was prepared using the general procedure C as light brown solid (52 %), MS: m/e= 489 (M+H). Example 303 4-lfBis-f2-emoxv-etnvi)-ainmo1-memyl4N-lf4- 2-yO-benzamide Using 4-chloromethyl-benzoyi chloride and bis-(2-emoxy-ethyi)-amine me title compound was prepared using the general procedure C as light brown solid (49 %), MS: m/e=543(M+H+). Example 304 4-lff2-Emoxy-etii4Vmeth.)d-ammo]-met3i4}-N-f4-memoxy-7~morpholin-4-4- benzotfaiazol-2-yiVbenzamide Using 4-chloromethyl-benzoyl chloride and (2-emoxy-ethyl)-memyI-arnine the title compound was prepared using the general procedure C as white solid (78 %), MS: m/e= 485 (M+rT). Example 305 N-( 4-Memoxv-7-mnrplin1in-4-vi-benzothiazoI-2-yi")-4-f 4-methoxy-pip eridin-l -yl - methvD-benzamide Using 4-chloromethyl-benzoyl chloride and 4-methoxy-piperidine the title compound was prepared using the general procedure C as white solid (33 %), MS: m/e= 497 (M+H). Example 306 4-Diethyla minompthvl-N- (4-methoxy-7-morpholm-4-vi-benzothia2ol-2-vi yhmramiAr Using 4-clilorometh.yl-benzoyl chloride and diethylamine the title compound was prepared using the general procedure C as light yellow solid (64 %), MS: m/e= 456 (M+H). Example 307 4-f(2-Methoxy-ethy1ammoVmemyll-N-f4-mefooxv-7-m Using 4-chloromethyl-benzoyl chloride and 2-memoxy-ethylarnme the tide compound was prepared using the general procedure C as white solid (64 %), MS: m/e= 457 (M+H). Example 308 N-{4-Mefooxy-7-morpholm-4-vi-benzotfoazol-2-yD-44 benzamide Using 4-chloromethyl-benzoyl chloride and 2-methyl-lH-imidazole the title compound was prepared using the general procedure C as white solid (87 %), MS: m/e= 464 (M+H). Example 309 N-(4-Memoxy-7-momhoHn-4-4-ber4othiazol2-Yl)-4-f4-4 bn?anwjk Using 4-chloromethyi-benzoyl chloride and 1-methyl-piperazine the title compound was prepared using the general procedure C as white solid (78 %}, MS: m/e= 482 (M+H). Example 310 N-(4-Memoxy-7-moipholm-4-yl-ben2ntiiia2X>I-2-yl4 Using 4-chIoromethyi-benzoyi chloride and pyrrolidine the title compound was prepared using the general procedure C as white solid (81%), MS: m/e= 454 (M+H). Example 311 N-f4-Metfaoxy-7-moTph™K"4-yi-benzotniazol-2-ffi Using 4-chloromethyl-benzoyl chloride and morpholine the tide compound was prepared using the general procedure C as white solid (83%), MS: m/e= 469 (M+H). Example 312 N-(4-Ber4loxy-7-morpholfo4-yl-benzotliiazol-2-ylM-44 amino] -methvlt-benzamide Using N-(4-benzyloxy-7-morpholm4yl-benzotn4 and (2-memoxy-ethyl)-methyl-ainine the title compound was prepared using the general procedure C as white solid (69 %), MS: m/e= 547 (M+lT). Example 313 N-(4-Metfaoxy-7-morpholm4-Yl-benzothia2ol-2-4 ammol-methyll-benzamide; hydrochloride N-(4-Methoxy-7-morphofo4-yI-benzothiazaI-2-yl)4-4 {100 mg> 0.24 mmol), triethylamine (35 mg, 0.34 mmol), potassium iodide (0.4 mg, 0.02 mmol) and 333-trifluoro-rnropylaniine (48 mg, 0.27 mmol) were dissolved in ethanol (1 ml) and dioxane (0.5 ml). The reaction vessel is sealed and heated to 90°C for 18 h. Workup and purification as described in the general procedure C afforded the tide compound as light brown solid (28 %), MS: m/e= 509 (M+tT). Example 314 4-(2-Memoxv-ed4xvmedivlVN-(4-memoxv-7-morpholm4vl-benzothiazol-2-4d)-benzamide 4-L4aromemyl-N-(4-methoxy-7-morpaoIm-4-yl-bei4 (200 mg, 0.48 mmol) and sodium hydride (42 mg 55 % dispersion in mineral oil, 0.96 mmol) were dissolved in 2-methoxy-ethanol (3.8 ml, 48 mmol) and stirred at ambient temperature for 18 h. Workup and purification as described in the general procedure C afforded the title compound as white solid (70 %), MS: m/e= 458 (M+H+). Example 315 4-Memoxvrnem4-N-(4-memoxy-7-moipholm4-yl-b£n2othiazol-2-yl)-bfflMrniH4 4-C4oromethyl-N-(4-methoxy-7-morpholm4-yI-beri2omiazol-2-yl)-benzamide (200 mg, 0.48 mmol) were suspended in THE (5 ml) and sodium methoxide (0.27 ml 5.4 M in MeOH, 1.4 mmol) were added at 0 °CThe mixture was stirred at ambient temperature for 18 h. Workup and purification as described in the general procedure C afforded the title compound as light yellow solid (41 %), MS: m/e= 414 (M+H). Example 316 N- f 4-Methoxv-7- (l-oxo-lX4-thiomorpholm-4-Ti)-benzothiazol-2-,yll-heTi7aTnidf? To a solution of N-(4-memoxy-7-thiomorpholm4-yl-ben2othia2oI-2-yi)-beraamide (80 mg, 021 mmol) in [l,4]dioxane (3 ml) was added sodium periodate (89 mg, 0.42 mmol) and the mixture stirred for 20 h at ambient temperature. To this mixture water (10 ml) and dichloromethane (10 ml) were added, the phases were separated and the aqueous layer extracted twice with dichloromethane. The combined organic extracts were dryed with Na2S04 and the solvent evaporated. Recrystallization from hot THF afforded the title compound as white solid (21 %), MS: m/e= 402 (M+rT). Example 317 N-U-MetbnYY-7-thiomorpholin-4-Yi-ben7.nt>iia7.ol-2-vl")-benzamide Following the general method of example 403 the title compound was synthesized from 3-(2-memoxy-5-miomorphoHn-4-yl-phenyl)-tmourea (synthesized from 4-bromo-l-memoxy-2-nitro-benzene and thiomorpholine as described for l-benzoyl-3-(2-methoxy-5-morpholin-4-yl-piienyl)-thiourea) as a white solid (15 %), MS: m/e= 386 (M+H"). Example 318 5-Medivi-thiophene-2-carbpxylic acid (4-methoxy-7-piperazin-l-yl-hpn7irthiazol-2-yi)-amide To asolution of4-{4-memoxy-2-[(5-methyl-tHophene-2-caibonyi)-aniino]-benzothiazol-7-yl}-piperazine-l-carboxyl£c acid benzyl ester (300 mg, 0.57 mmol) in dichloromethane (5 ml) were added boron trifluoride diethyl etherate (0.72 ml, 5.7 mmol) and ethane thiol (1.2 ml, 17 mmol) and the mixture stirred for 36 h. The volatile components are evaporated and the residue codistilled twice with toluene. The residue was dissolved in dichloromethane (25 ml), extracted with IN aqueous sodium carbonate and the organic phase dryed with NajSO Removal of the solvent and flash chromatography (silica, eluent CHzCb/MeOH/aqu. NH4OH 100:10:1) afforded the title compound as light yellow solid (58 %), MS: mJe= 389 (M+H+). Example 319 5-Methyl-tbinphene-2-carboxvlic acid [7-("4-acetyl-pipera2in-l-vl)-4-metho%y-benzomiay-ol-2-vll -amide 5-Methyl-truophene~2-carboxylic acid (4-methoxy-7-piperazm-l-yi-benzotlnazol-2-yl)-amide (100 mg, 0.26 mmol) were suspended in DMF (2 ml) and treated with acetyl chloride (22 \A, 0.30 mmol) and pyridine (27 ul, 0.34 mmol) and the mixture stirred for 5 h at ambient temperature. Workup and purification as described in the general procedure C afforded the product as a white solid (55 %), MS: m/e= 431(M+H). Example 320 4-{4-Memoxv-2-[f5-memvl-thiophene-2-caThnTiy14ammn]-hpn7otihiazn]-7-vll-pippra7ine-l-carboxvlic acid methyl ester Using methyl chlorofbrmate the tilte compound was synthesized as described for example 319 and obtained as white solid (26 %), MS: m/e= 447(M+H+). Example 321 5-Methvi-thiopbene-2-carboxylic acid [4-methoxy-7-f4-methyl-piperawn-l -vD-benzothiazol-2-yn -amide To a solution of 5-methyl-tbiophene-2-carboxylic acid (4-methoxy-7-piperazhi-l-yi-benzothia2ol-2-yl)-arnide (100 mg, 0.26 mmol) in methanol (8 ml) were added formic acid (100 ul, 2.6 mmol) and formaldehyde (23 ul, 0.31 mmol) and the mixture refluxed for 18 h. Workup and purification as described for 5-methyl-thiophene-2-carboxyiic acid (4-memoxy-7-prperazm-l-yI-benzothiazol-2-yi)-arnide afforded the product as light yellow powder{34-%), MSrrak«=4f»(14+f1">. Eyaaspte-323 5-Methyl-tbJophene-2-carbogidic acid \ 7-f2,3-dihvdro-lH-indol-6-yl)-4-inetlioxy- ben7othta?oi-2-yi 1-amide The tide compound was prepared from 5-methyl-thiophene-2-carboxylic acid (7-iodo-4- memoxy-benzothiazol-2-yl)-amide (100 mg, 0.23 mmol) and 6-iodo-23-dihydro-lH- indole using the general procedure B in Example 54 as light brown crystals (26 %), MS: m/e=422(M+Hf). Intermediate 4r(4-Beri24oxv-3-nitro-phenYl)-rnorpb.oline The tide compound was prepared using morpholine and l-benzyloxy-4-bromo-2-mtro-benzene (prepared from 4-bromo-2-nftro-anisol and benzyl bromide) using the general method of example ""4-(4-memoxy-3-nitro-phenyI)-morpholinen as yellow solid (58 %\ MS: m/e= 315(M+H+). Intermediate ?.- A mini->-4-morphnHTi-4-yl-phenol Catalytic hydrogenation of 4-(4-benzyloxy-3-nitro-phen"yl)-morpholine (5 g, 16 mmol) in dichloromethane (500 ml) and ethanol (500 ml) using palladium on carbon (500 mg, 10%) afforded the title compound as a grey solid (96 %), MS: mVe= 194(M+). Example 323 N-f4-HydroxyT7-rnnTpbolin-4-vi-beri20thiazol-7.-y1)-KpTi7aTTii4p The title compound was prepared using 2-arriino--4-morpholin-4-yl-phenol as described for N-(4~rnethoxy-7-morpholm4yl-benzothiazol-2-yl)-benzamide and obtained as a light brown solid in 14 % overall yield, MS: m/e= 356(11+11). Example 324 5-MedwJ-thiophene-2-carboxyHc acid f7-f3-dimethy1amir>f>-pyiTolidip-l-yl)-4-methoxy-benzothiazoI-2-yi] -amide Using 5-methyI-thiophene-2-carbonyl chloride and 7-(3-dimethylamino-pyrrolidui-l-yl)-4~methoxy-ben2X)thiazol-2-yl-amine the tide compound was prepared using die general method of example 1 as yellow solid (90 %), MS: m/e= 417 (M+fT). Intermediate 7- (3-Dlmethylamino-pyrroudin-1 -vl44methoxv-t)enzothia7Jol-2-yl--amine Following the general method of example 403 the title compound was synthesized from [5-(3-dimemylarm4o-ptyrrolidin-l--yl)-2-methoxy-phenyl] -thiourea (synthesized from 4-bromo-l-methoxy-2-nitro-benzene and dimethyI-rjyrrou"dm-3-vl-arnine as described for (2-methoxy-5-morpholin-4-yl-phenyl)-thiouxea) as a white solid (25 %), MS: m/e= 293 (M+rT). Example 325 Tetrah.ydro-pvran-4-carboxyIic acid f4-methoxy-7-morpholin-4-yl-benzothiazol-2-ylV amide To a solution of 2-anuno4memoxy-7-morphoIm-4r-yl-benzothia2ol (100 mg, 0.4 mmol) in tetrahydrofiirane (2 ml) were subsequently added N-emylniiisopropylamine (194 Q, 1.1 mmol) and tetrah.ydropycan-4-caibonyl chloride (77 mg, 0-52 mmol, dissolved in 0.5 ml tetrahydromrane) and the mixture refluxed for 3 h. The mixture was then cooled to 0°C methanol (0.4 ml) was added and the mixture slowly warmed to 20 C. Then the mixture was evaporated to dryness, dichloromethane was added (3 ml) and extracted with saturated aqueous sodium carbonate. After back extraction of the aqueous phase with two portions of dichloromethane (3 ml), the combined organic phases were dryed with Na2S04 and the solvent evaporated. The crude product was was then chromatographed over SiO4 eluting with CH2Q2/MeOH 98:2, the product fractions were pooled and the solvent evaporated, to afford the title compound as a beige powder (142 mg, 76 % yield), MS: m/e= 378(M+H+). Following the general method of example 325 the following examples were prepared Example 326 4-(4-Memoxy-7-morpholm4yl-benzothia2oI-2-vlcart acid tert-butyi ester Using 2-ammo-4-memoxy-7-morphoIm-4-yi-benzothiazoI and 4-chlorocarbonyI- piperidine-1 -carboxylic acid tert-butyl ester the title compound was obtained as a white solid (3 %), MS: m/e= 477(M+rT). Example 327 l-Acetyl-piperidine-4-carboxviic acid f4-melhoxy-7-moipholm-4-vl-benzothiazol-2-vl)-amide Using 2-amino-4-methoxy-7-moipholin-4-yl-benzothiazol and l-acetyl-piperidine-4-carbonyl chloride the tide compound was obtained as a white solid (22 %), MS: m/e= 419(M+rT). Example 328 Piperiduie-4-carboxyiic add (4-methoxy-7-morpholin-4-vl-ben2othiazol-2-vi)-.atntHf 4- (4-Methoxy-7-moipholm4-yl-beriZotbiazol-2-ylcarbamoy!)-piperidine-l -carboxylic add tert-butyl ester (95 mg, 0.2 mmol) were dissolved in trifluoroacetic add (0.8 ml). After 1 h at room temperature, the mixture was evaporated to dryness. Purification as described for tetrahydro-pyran-4-carboxylic add (4-metboxy-7-morphoh44yl-benzotbiazol-2-yl)-amide afforded the title compound as a white solid (77 %), MS: m/e= 377(14+14). General procedure E (ureas): The appropriate substituated 2-amino-benzothiazol (1 part, typically 500 mg) is dissolved in CH2CI2 (100 parts) and treated with pyridine (3 parts) and phenyl chloroformate (1.25 parts). After stirring for 30 min at room temperature the mixture is remixed for 2 h when the appropriate amine (5 equivalents) is added. After refluxing for 18 h, the mixture is evaporated to dryness, dissolved in CH2Q2 and extracted with aqueous sodium carbonate, after back extraction of the aqueous phase with CH2O2 the combined organic layers were dried with NaaSO, and evaporated to dryness. The product is isolated by flash chromatography (silica, eluent dichloromethane containing 23 % methanol). Following the general method E the compounds of examples 329 to 367 and Example 370 were prepared Example 329 4-r(4-HuorcH-phenvIammo)-methvl1-piperidine-l-carboxylicaddf4-methoyy-7- morphoh4n"4--yl--benzothiazoI-2-yI)-arnide Using 4-memoxy-7-morpholm-4-yl-ben2otbia2ol-2-ylamine and 4- [(4-fluoro- phenyiamino)-methyl]-piperidine the title compound was obtained as off-white solid (25 %). MS: m/e= 522 (M+H). Example 330 4rHydrQxymethy4-4-phenvi-pip4ridinp-1 -carboxylic add f4-methoxy-7-morphfilin-4-vl- Using 4-meliiosy-7-morpholin4yl-beiKotiu4ol-2-yiainiiie and 4-hydroxymethyl-4-phenyi-piperidine the title compound was obtained as light yellow solid (50 %). MS: m/e= 483 (M+H+). Example 331 f l-("4-Methoxy-7-moi4holm4-yl-benzQthiazoi-2-yi-carbaiHoyl )-piperidin-4-ylTnet4y{ ] - carbaroic acid metbyl ester Using 4-memoxy-7-moiphottn-4-yl-benzotm4ol-2-yl-amine and piperidin-4-yhnethyl- carbamic acid methyl ester the title compound was obtained as white solid (81 %). MS: m/e=464(M+H+). Example 332 4-Ethvl-piperidine-l-carboxvlic acid f4-methoxy-7-morpholin-4~yi-benzomiazol-2-yi)-amide Usnlg4-methoJ4-7~mo4phoIm-4-yJ-be42X)tm"a2o42-yianline and 4-ethyI-piperidine the title compound was obtained as white solid (26 %). MS: m/e= 406 (M+H). Example 333 4-(2-Oxo-pvrroHdin-l-yhTiethyl4-piperidine-l-carboxylic add (4-methoxy-7-morpholin- 4-yl-benzothiazol-2-yiVamide Using 4-methoxy-7-morpholm4-yi-benzotiiazol-2-yl-amine and 4-(2-oxo-pyrroHdin-l- yimethyi)-piperidine the title compound was obtained as white solid (29 %). MS: m/e= 474 (M+H1"); Example 334 4-(2-Methoxy"ethyl)-pipera7ine-l-cafboxyUc add (4-methoxy-7-morpholin-4-yl-hf>n7.nthinzoU2 -yP-amide Using 4-methoxy-7-morphonn4yl-benzotmazol-2-yl-aiiiine and 4-(2-methoxy-ethyl)-piperazine-the title compound was obtained as off-white solid (79 %). MS: m/e= 437 (M+H+). Example 335 4-Cranometfa4-piperidme-l-carbox4ic acid (4-metiioxr-7-morpholin-4-yi-bena3thiazol-2-vJ")-amide Using 4-memoxy-7-morphoiin4yi-ben20thiazol-2-yl-amine and 4-cyanomethyl-piperidine the title compound was obtained as white solid (46 %). MS: m/e= 416 (M+H1"). Example 336 [ 1-f 4-MethoCT-7-morpholin44-benzothia2ol-2-4Karbanio4)-piperidin4TdmetfaTrfl -carhapic acid tert-butyl ester Using 4-memoxy-7-morphoh44-yI-benzothiazoI-2-yl-amine and piperidin-4-ylmethyI-caibamic acid tert-butyl ester the title compound was obtained as white solid (11 %). MS: m/e= 506 (M+H). Example 337 4-f2-f"4-CbJoro-phen}dVtetiahydro"njran-241-piperidine4l 7-morpholin-4-yl>ben7fithia7.ol-2-yl")-aniide Using 4-methoxy-7-morphoh44yl-benzo1m4zol-2-yl-aniine and 4-[2-(4-chloro-phenyl)- tetrahydro-f«xan-2-yl]-piperidine the title compound was obtained as white solid (43 %). MS:m/e=557(M+H+). Example 338 4-(2-Hydroxv-edi4)-piperidine-l-carboxylic acid f4-merooxy-7-morpholin-4-Tl-benzothrazoJ-2-vi )-amide Using 4-memoxy-7-morpholm4yl-benzomiazol-2-yl-amine and 4-(2-hydroxy-ethyl)-piperidine the title compound was obtained as white solid (64 %). MS: m/e= 421 (M+H). Example 339 l-(2-Mefoo:xy-emylV34f4-memoxy-7-morpholm44 Using 4-methoxy-7-morpholm4yl-benzotbia2ol-2-yl-amine and (2-methoxy-ethyl)- methyi-amine the tide compound was obtained as white solid (65 %). MS: m/e= 381 (M+H). Example 340 4-Methoxyacetvi-piperazine-1-carbo3iylic acid f4-methoxv-7-morpholin-4-Ti- benzot4ia7J)l-2-yl1-amide Using 4-methoxy-7-morpholm4yl-ben20thiazol-2-yl-amine and 4-methoxyacetyl- piperazine the title compound was obtained as beige solid (84 %). MS: m/e4 450 (M+H). Example 341 4-Methvi-pippn, amide Using 4-metiioxy-7-morphoIm-4-yi-faenzothiazoI-2--yl-annne and 4-methyl-piperidine the title compound was obtained as white solid (47 %). MS: m/e= 391 (M+H). Example 342 4-Oxo-piperidine-l-carboxviic acid (4-methoxy-7-morpholin-4-4d-benzothiazol-2-vD- arnitfe Using 4-methoxy-7-moipholm-4-yl-benzotniazol-2-yI-ainine and piperidin-4-one the title compound was obtained as white solid (38 %). MS: m/e= 391 (M+fT). Example 343 4-Cydopropyl-4-hydroxy-piperidine-l-carboxviic acid C4-methoxy-7-morphoHn-4-yl- benzothiazol-2-yi)-amicie Using 4-meliioxy-7-moi7hoIm4-)4-beiizothiazol-2-7l-amine and 4-cyclopropyi-4- hydroxy-piperidine the title compound was obtained as white solid (27 %). MS: m/e= 434 (M+iV). Example 344 l.I-Dioxo-l4-thiomorphol4f-4farboxylic acid (4-methoxy-7-morpholin-4-yi- benzothiazol-2-yl")-amide Using 4-methoxy-7-morpholm-4-yl-ben20tbiazol-2-yl-ainine and tbiomorpholine 1,1- dioxide the title compound was obtained as white solid (50 %). MS: m/e= 427 (M+H). Example 345 4-HvdroxvmethyI-piperidine-l-carboxvu"c acid t4methoxy-y-morpholin4-yl- benzothia7r>1-7.-yl"l-amiHe Using 4-melkoxy-7-morphoUn-4~yl-benzoliiiazol-2-ylamine and 4-hydioxymetbyi- piperidine the title compound was obtained as white solid (31 %). MS: m/e= 407 (M+H1-). Example 346 Octahydto-quinoline-l-caiboxyiic acid (4-methoxv--7-morpb,olin-4-yl-benzothiazol-2-ylV amide Using 4-metho4-7-inorphQUn4yi-benzo1ii4ol-2-yl-amine and octahydro-quinoline the tine compound was obtained as white solid (79 %). MS: m/e= 432 (M+K1-). Example 347 2.3-Benzo-1.4-dioxa-8-a2a-spiror4.5ldecane-8-carboxvdic acid f4-methoxv-7-moTphnliTi- 4-yl-benzothiazol-2-yl)-amide Using 4-methoxy-7-morpholin4yl-benzotinazol-2-yl-amine and 2,3-benzo-l,4-dioxa-8- aza-spiro[4,5]decane the tide compound was obtained as white solid (63 %). MS: m/e= 483 (M+H). Example 348 4-f 4-Metfaosy-7-g]orpIioJin-4-v3-benzomiazo]-2-vi-carbamoy] )-piperazme-1 -carboxyiic acid methyl eyter Using 4-methoxy-7-morpbolin4-yl-benzothiazol-2-yl"amine and piperazine-1-carboxyfic acid methyl ester the title compound was obtained as white solid (90%). MS: m/e= 436 CM+H). Example 349 Octahvdr"-i"!rtq»"noline-2-carboxylic acid f4-methoxy"7-morpholin-4-yl-benzothiazol--2- yl)-amide Using 4-methoxy-7-moipholin4yl-benzotbiazol-2-yl-amine and octabydro-isoquinoline the title compound was obtained as white solid (53%). MS: m/e= 432 (M+H). Example 350 3-Methyi-piperidine-l-caiboxylic acid (4-methoxy-7-morphoIin-4-yl-hen7nfhia7ol-2-yl)- amide Using 4-memoxy-7-mc4holm4yl-benzounazol-2-yl-aniine and 3-methyl-piperidine the title compound was obtained as white solid (50 %). MS: m/e= 391 (M+H1"). Example 351 3-HvdroxymethTi-piperidine-l-carboxvlic acid f4-memoxy-7-morpholin-4-yl-benzothiaanl -2-yl)-aTnide Using 4-methoxy-7-morphoIm-4~yl-benzothiazoI-2-ylaraine and 3-hydroxymethyl-piperidine the title compound was obtained as white solid (69 %). MS: m/e= 436 (M+H). Example 352 3>4-Benzo-l~oxa-8-aza-spiio[4.5]decane-8-carboxyiic acid f4-methoxy-7-mnrphnlin-4-vl-benzothiazol-2-vl-amide Using 4-metbxixy-7-morpholm-4-yl-benzotiuazoI-2--yl-amine and 3,4-benzo-l-oxa-8-aza-spiro[4.5]decaue the title compound was obtained as light yellow solid (67 %). MS: m/e= " 481 (M+H). Example 353 4-(4-Methoxy-7-morpholin-4-yl-benzomiazoI-2-yl-carbamov1 4-pipwazine- l-carboxylic acid tert-bntvi ester Using4-methoxy-7-moipholm-4-yl4>enzotMazol-2-yl4 acid fert-butyl ester the title compound was obtained as light yellow solid (66 %). MS: m/e= 478 (M+H1"). Example 354 4-Hvdroxv-4-phenY4-piperidine-l-carboxylic acid f4-methoxv-7-morpholin-4-yl- benZ0tbia7n1-?--v11-amidft Using 4-methoxy-7-mcopholm-4-yl-benzot3iiazol-2-yl-aniine and 4-hydroxy-4-phenyl- piperidine the title compound was obtained as light yellow solid (36 %). MS: m/e= 469 (M+H). Example 355 4-Methyi-piperazine-l-carboxylic acid (4-memoxy-7-morpholin-4-yl-ben2othiazoI-2-viV amide Using 4-rnethoxy-7-morpholm-4-yl-benzotbJaMl-2-yl-ainine and 4-methyl-piperazine the title compound was obtained as beige solid (20 %). MS: m/e= 392 (M+H1"). Example 356 4-Trifluorometh4-pippridine-l-carboyylic acid f4-methoxv-7-morphoIin-4-yl- benzotbTa7r>l-2-yl)-aTnidp Using 4-methoxy-7-morpholm-4-yl-berizotiua741-2-yl-amine and 4-trifIuoromethyI- piperidine the title compound was obtained as white solid (16 %). MS: m/e= 445 (M+H4"). Example 357 f l,4"1Bipiperidmyl-l"-carboxylic acid f4-methQJCV-7-morphnlTn-4-yl..benzothiazol-2-ylt- amide Using 4-metJaoxy-7-moi4holin4yl-benzothiazol-2~yl-amine and [l,4"]bipiperidinyl the title compound was obtained as white solid (35 %). MS: m/e= 461 (M+H). Example 358 3-(4-Methoyy-7-morpholiD-4-vi-benzothiazoI-2-4V 1- (4-methoxy-phenyO- 1-methyi-urea Using 4-metho4-7-morphoUc-4-yl-benwtliiazol-2-yi-amine and 4-methoxy-phenyl}-methyl-amine the title compound was obtained as light yellow solid (40 %). MS: m/e= 430 (M+JT). Example 359 L4-Diosa-8-aza-spiror4.5ldpraDe-8-carbox)dicaddf4-methoxv-7-moi7jbrt1in-44yl-beazotbiazol-2-vD-amide Usmg4-methoxy-7-moiphohn-4-yl-ben20thiazol-2-yl-amuie and l,4-dioxa-8-aza-spiro [4,5] decane the title compound was obtained as beige solid (28 %). MS: m/e= 435 (M+H1"). Example 360 3.4-Dihvdro-lH-isoquinoline-2-catboxylic acid (4-methoxv-7-morpholin-4-yl- benzothiazol-2-yl)-amide Using 4-methoxy-7-morpholm4yl-ben20tbJazol-2-yl-amine and 1,2,3,4-tetrahydro- isoqumoline the title compound was obtained as orange solid (63 %). MS: m/e= 425 (M+fT). Example 361 3-f 4-Methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-l -methyl-1 -phenyl-urea Using 4-methoxY-7-morpholm-4-yl-benzotWazol-2-yl-anTine and methyl-phenyl-amnie the title compound was obtained as white solid (19 %). MS: m/e= 399 (M+H1"). Example 362 4-Hvdroyy-piperidioe-l-carboxylic acid l"4-methoxy-7-morpholin-4-vl-ben7-ntliiazol-2-y?)-amiHg Using 4-memoxy-7-moipholm-4-yl-benzothiazol-2-Yl-arnine and piperidin-4-ol the title compound was obtained as yellow solid (50 %). MS: m/e= 393 (M+H). Example 363 4-Memoxy-piperidine-l-carboxviic acid (4-methoxy-7-morpholin-4-yi-benzotbia2oI-2- yl)-amide Using 4-methoxy-7-morpholm4yl-beii20tbia2ol-2-yI-atDine and 4-methoxy-piperidine the title compound was obtained as yellow solid (33 %). MS: m/e= 407 (M+H), Example 364 l-Oxo-ll4-thTQinorpholine4carboxylic acid f4-memoxy-7-moipholin-4-yl-hffn7.nthia7.nl- 2-vP-amide Using 4-memoxy-7-morpholm-4-yl-benzothiazol-2-yl-ainine and thiomorpholine 1-oxide the tide compound was obtained as white solid (87 %). MS: m/e= 411 (M+H). Example 365 Methanesulfonic acid l-(4-memoxy-7-moipholm-4-yl-benzothiazol-2-yIcarbamoTl)" piperidm-4-yl-metbyi ester 4-Hydroxymethyl-piperidine-l-carboxylic acid (4-methoxy-7-morpholin-4-yl- benzotbiazol-2-yi)-amide (300 mg, 0.43 mmol) andN-ethyldiisopropylamine (95 pi, 0.56 mmol) were dissolved in CH2Q2 (10 mi), mefhanesulfonyl chloride (36 ul, 0.47 mmol) was added and the mixture stirred at ambient temperature for 3 days. Purification as described in the general procedure E afforded the product as a white solid (34 %) MS: m/e= 466 (M+fT). Example 366 Piperazine-1-carboxyiic acid f4-methoxv-7-morpholip-4-yl--beDzothia7nl-2-Yl)-3miHe Following the general method for piperidine-4-carboxyhc acid (4-methoxy-7-morphoUn-4-yi-beri7x)thiazol-2-yl)-amide the title compound was prepared from 4-(4-methoxy-7-rnorpholin-4-yl-benzo1hia2ol-2-yl-carbamoyl)-pipera2ane-l-carboxyHc acid tert-butyl ester as a light yellow solid (99 %).MS: m/e= 378 (M+H). Example 367 4-Aminomethyl-piperidine-l-carboxyUc acid (4-memoxy-7-morpholin-4-y4-b Following the general method for piperidine-4-carboxylic acid (4-methoxy-7-morpholin- 4-yl-benzothiazol-2-yl)-amide the title compound was prepared from [l-(4-methoxy-7- morpholm-4-yl-berizotmazol-2-yl-carbamoyl)-pipOT acid tert- butyl ester as a white solid (50 %) JvIS: m/e= (M+H4"). Example 368 (4-Mefeoxy-7-morpholin4vl-benzothiazol--2-ylVcarbamic acid 2-methoxy-ethyl ester 4-Methoxy-7-mc«phonB4y/-berizotiuazof-2-yl-amme (300 mg, 1.1 mmof) and N-ethyldiisopropylamine (0.56 ml, 3.4 mmol) were dissolved in tetrahydrofurane (11 ml) and 2-methoxyethyl chloroformate (0.19 ml, 1.4 mmol) were added over 5 min. Then the mixture was heated to 70 °C for 3 h. The mixture was cooled to room temperature, water added and extracted twice with ethyl acetate. TRhe combined organic phases were dryed with Na2S04 and evapprated to dryness. The title compound was obtained as off-white solid (52 %). MS: m/e= 368 (M+H4"). Example 369 J.4- (4-Methoxv-7-morpholin-4-yl-benzothiazoI-2-yicarbamoT4)-benzyl] -methyi-carhaTnic add methyl ester N-(4-Memoxy-7-moi4hohn-4-yi-benzothiazol-2-4 (100 mg, 0.24 mmol), pyridine (29 ul, 0.36 mmol) and methyl chloroformate (24 jd, 0.32 mmol) were dissolved in dichloromethanel (5 ml) and stirred at ambient temperature for 18 h. Workup and purification as described in the general procedure C afforded the title compound as light yellow solid (66 %), MS: m/e= 471 (M+fT). Example 370 l-Oxo-lXj-thiomorpholine-4-carboxviic acid f4-memoxy-7-piperidm-l-yi-benzotbia2ol-2-vP-amide hydrochloride Using 4-memoxy-7-piperidm-l-yl-benzouHa2»l-2-ylamine and tbiomorpholine 1-oxide the titie compound was obtained as white solid in accordance with general procedure E (80 %). MS: m/e= 409 (M+H). Example 371 N-(4~Emoxy-7-piperidm-l-vl-benzot+jia2ol-2-vlM-fluoro-ben2ajnide The title compound was prepared strarting from 4-bromo-l-ethoxy-2-nitro-benzene and piperidine as described for 4-fluoro-N-(4-memoxy-7-morphoh4-4-yl-beri20thiazol-2-yI)- benzamide (Example 275) and obtained as a yellow solid in 10 % overall yield, MS: m/e= 400 (M+H1"). Example 372 l-Huoro-N-(4-isopropoxy-7-piperidin-1 -y!-beiizotMazoI-2-yI)-hf»n?smirip Ihe title compound was prepared strarting from 4-bromo-l-isopropoxy-2-riitro-benzene and piperidine as described for 4-fiuoro-N-(4-meaioxy-7-moiphoun4yi-benzothiazol-2-yl)-benzamide (Example 275) and obtained as a light brown solid in 10 % overall yield, MS: m/e= 414 (M+lT). Example 373 4-Fluoro-N-(4-memoxy-7~pyrroHdin- l-yl-benzolhiazol-2-yl VhCTi7amiH The title compound was prepared strarting from 4-bromo-l-memoxy-2-nitro-benzene and pyrrolidine as described for 4-fluoro-N-(4-methoxy-7-morpholin-4~yI-benzothiazoI-2-y5)-benzamide (Example 275) and obtained as a light brown solid in about 10 % overall yield, MS: m/e= 372 (M+H+). Example 374 4-Ruoro-N-f4-memoxy-7-[l,4loxazepan4yl-benzothia?ol-2-yiVbenMiniHf» The title compound was prepared strarting from 4-bromo-l-methoxy-2-nitro-benzene and [1.4]Gxazepane as described for 4-fluoro-N-(4-memoxy-7-morpholin-4-yI-benzothiazol-2-yl)-benzamide (Example 275) and obtained as a light yellow solid in about 10 % overall yield, MS: m/e= 402 (M+H+). Example 375 Morpholine-4-carboxyiic acid l4-memoxv-7-f4-methoxy-piperidin-l-vlVbenzo1hia2ol-2-yH -amide The tide compound was prepared strarting from 4-bromo-l -methoxy-2-nitro-benzene and 4-methoxy-piperidine as described for morpholine-4-carboxylic acid (4-methoxy-7-morpholin-4-yl-ben2othia2ol-2-yl)-amide (Example 136) and obtained as a light yellow solid in about 10 % overall yield, MS: m/e= 407 (M+H+). Example 376 N- (7-Azepan-1 -yl-4-methoxv-benzothiazol-27yl) -4-nrtro-benzamide The title compound was prepared using 4bromo-l-met&oxy4-nitro-benzene, azepane and 4-nitro-benzoyl chloride as described for 4-fluoro-N-(4-methoxy-7-morpholin-4-yl- benzothia2ol-2-yI)-benzamide (Example 275) and obtained as a light yellow solid in about 10 % overall yield, MS; m/e= 427 (M+H). Example 377 Morphnline-4-carboxvlic acid f4-methoxv-7-thiophen-3-yl-benzothiazol-2-Yl)-amide The title compound was prepared strarting from 4-bromo-l-memoxy-2-nitro-benzene and trimethyl-thiophen-3-yl-staruiane as described for morphoIine-4-carboxylic acid (4-methoxy-7-phen)d-benzothiazol-2-yl)-amide (Example 157) and obtained as alight yellow solid in about 10 % overall yield, MS: m/e= 376 (M+H+). Example 378 4-Fluoro-N- \ 4-methoxy-7- (2-methyi-irDidazoI- l-vlVbenzothiazol-2-yll -hwi?ami4 N-(7-Acetylann4o4methoxy-benzothia2ol-2-yl)4-fluoro-benzamide (100 mg, 0.28 mmol) and Lawessons reagent (135 mg, 0.33 mmol) were dissolved in THF (10 ml) and stirred at ambient temperature for 18 h. Removal of the solvent and flash chromatography (silica, eluent CH2Cy2N aqu. NH3 in MeOH 99:1 to 19:1) afforded a yellow solid which was dissolved in acetone (10 ml) and treated with iodomefhane (19.8 mg, 1.4 mmol). After 3 h at ambient temperature the solvent was removed and after dissolution in ethanol (10 ml), aminoacetaidehyde dimethyl acetal (15 mg, 1.4 mmol) were added and the mixture stirred for 18 h at room temperature. The solvent was removed and the residue refluxed for 24hin ethanol (10 ml) and cone sulfuric acid (1 ml). Theniixture was diluted with, water (50 ml) and the pH adjusted to 8 with sodium carbonate. It was extracted three times with dichloromethane. The combined organic extracts were dryed with sodium sulfate and the solvebt removed. Flash chromatography (silica, eluent CH2CI2/2N aqu. NH3 in MeOH 96:4 to 9:1) afforded the title compound as brown solid, MS: m/e= 383 (M+rT). Example 379 2-Chloro-N-(4-memoxy-7-morpholm-4-yi-bgr4 To a stirred suspension of 4-metJioxy-7-morphoh44yl-benzothiazol-2-yl-amine (13.3 g, 50.1 mmol) in THF (700 ml) was added JV-emyldiisopropylamine (21.3 ml, 125 mmol). The mixture was then cooled to 5 °C and a solution of 2-chloro-6-methyl-isonicotinoyl chloride (10.5 g, 55.1 mmol) in dichloromethane (350 ml) was added dropwise over 2 hours. The reaction mixture was then stirred overnight at 20 °C. To this mixture was added r4ffthflTini (4Q ml) and gtirr-ipj. mjmitps. Tie mixture,was. then, concentrated in vacuo and the residue partitioned between ethyl acetate and saturated sodium bicarbonate solution. The organic phases were then dried over NajSCU and the solvent evaporated. The crude product was then chromatographed over SiC>2 (Merck 230-400 mesh) eluting with CH2CyMeOH (98:2), the product fractions were pooled and the solvent evaporated, to afford the title compound as a brown solid (16.0 g, 76 % yieid)s MS: m/e = 421 (MfdJ+H), 419 (M4CIJ+H). Following General Procedure E the compounds of examples 380 and 381 were prepared Example 380 (4-Methoxy-7-morpholin-4-vl-benzotluazol-2-yl)-urea Using 4-me1ioxy-7-morpholm-4-yl-benzothia2ol-2-yl-aiMine and ammonia the title compound was obtained as a white solid (20%), MS: m/e = 309 (M+H4). Example 381 (4-Memo34-7-morpholm-4r-vl-b€nzothiazoI-2-Yl)-rarhamif: acid phenyl ester Using 4-metboxy-7-morpholm-4yl-beiizothiazol-2-yl-arnine and without adding an amine the title compound was obtained as a white foam (75%), MS: m/e s 386 (M+H). Following the general method of example 379 the fallowing compound was prepared Example 382 2-Cmoro-N-f4-meraoxy-7-morpholm-4-vl-benzot4 Using 4-methoxy-7-morpholm-4-yl-benzotliiazol-2-yl-arriine and 2-chloro-isonicotinoyl chloride the title compound was obtained as a brown solid (59%), MS: m/e = 407 (Ufa}+H)t 405 Example 383 2-Iodo-N-(4-methoxv-7-morphnlin-4-Yl-benzotbia7n1 -?.-yl )-6-methyi-isonicotinamide To a stirred suspension of 2-cMoro-N-(4-methoxy-7-morpholm4yl-benzothiazol-2-yl)-6-methyl-isonicorinamxde (1.00 g, 239 mmol) in ethyl methyl ketone (10 ml) and dioxane (20 ml) were added sodium iodide (2.0 g, 13.3 mmol) and hydriodic acid (0.95 ml, 7.2 mmol, 57 % aqueous). The mixture was then beated at 100 "C for 96 hours. The mixture was then concentrated in vacuo and the residue resuspended in dichlorornethane and washed sequentially with saturated sodium bicarbonate solution, 0.1M sodium tiuosulfate solution, and saturated brine. The organic pbate-mtbea dried over NjSO» and the solvent evaporated. The crude product was then chromatographed over SiCb (Merck 230-400 mesh) eluting with CH2a2/MeOH (99:1 then 98:2), the product fractions were pooled and the solvent evaporated, to afford the title compound as a brown solid (80 mg, 7 % yield), MS: m/e = 511 (M+rT). Following General Procedure E the compounds of examples 384 and 385 were prepared Example 384 1 -Benzyl-3-(4-meu4oxy-7-morphoIin-4-yl-benzothiazol-2-yI)-1 -methyl-urea Using 4-methoxy-7-moipholm-4-yl-ben2X)thia2ol-2-yl-amine and N-benzylmethylanune the title compound was obtained as an off-white solid (94 %), MS: m/e = 413 (M+H1"). Example 385 3- (4-Memoxy-7-morphoUn-4-yl-benzothiazol-2-yl)-l -methyl- 1-phenethvl-uTfta Using 4-methoxy-7-morpholm-4-yl-benzolnia2»l-2-ylamine and N-methyl-2-phenylethyiamine the title compound was obtained as an off-white solid (53 %), MS: m/e = 427 (M+H1-). Following the general method of example 379 the compounds of examples 386 to 391 were prepared Example 386 N-(4-Memoxy-7-moiphomi-4-vl-ben2othiazol-2-yl)-2-pb£nyI-acetamide Using 4-methoxy-7-morplio]m-4-yl-ben2otbia2ol-2-yl-amine and phenylacetyl chloride the title compound was obtained as a light yellow soh"d (37 96), MS: m/e = 384 (M+H). Example 387 N"-(4-Memoxy-7-morphoIm-4-vI-benzothia2oI-2-yf)-Tff4Tw"r"r"arni"fIp Using 4-medioxy-7-morphoh4-4-yI-benzotiu4zoI-2-yl-amine and propionyl chloride the title compound was obtained as alight yellow solid (5 %), MS: m/e = 322 (M+H). Example 388 2-Memoxy-N-f4-memoxv-7-morpholm-4-y4-km7rtthia2al-2-yl)-a«4mifi.- Using 4-memoxy-7-morpholm-4-}d-benzothiazol-2-yI-amine and methoxyacetyl chloride the title compound was obtained as a light yellow solid (37 %), MS: m/e = 338 (M+H). Example 389 PfntaTinir acid f4-metiioxy-7-morpholin4yl-benzothia2ol-?-yl)-aTriiHp Using 4-methoxy-7-morpholm-4-yl-benzo1iuazol-2-yl-amine and valeroyl chloride the tide compound was obtained as a light yellow solid (48 %), MS: m/e = 350 (M+H+). Example 390 JV-(4-MetJioxv-7-morphouj4yi-benzothiazoi-2"yi)-isobutyramide Using 4-methoxy-7-rnorpholm4yl-bemotbiazol-2-yl-amuie and isobutyryl chloride the tide compound was obtained as a light yellow solid (8 %), MS: m/e - 336 (M+H). Example 391 4-f4-Melhcc4-7-morphcJm4yl-benzotbia2ol-2"yl)-3-pheni6-Dropionarriide Using 4-methoxy-7-morpholm-4-yl-benzolmazol-2-yI-ainine and 3-phenylpropionyl chloride the title compound was obtained as a light yellow solid (3 %), MS: m/e = 398 (M+H). Following General Procedure E the compounds of examples 392 to 396 were prepared Example 392 l-Benzyl-3-(4-mellioxy-7-moipholin4yl-benzothiazol-2-ylVurea Using 4-memoxy-7-morpholm-4-yl-benzothia2»l-2-yi-ainine and benzyiamine the title compound was obtained as an off-white solid (99 %), MS: m/e = 399 (M+H). Example 393 l:(4-Methoxv-7-moTpbolin-4-y1-hCT7.otMazol--2-,sd")-3-phenethyi-urea Using 4-memo4-7-morpholm4yl-benzotbiazol-2-yl-amine and 2-phenylethylamine die title compound was obtained as an off-white solid (87 %), MS: m/e = 413 (M+H). Example 394 T-f2-Methoicv-emvlV3-f4-methcocv-7-moroholm-4--4-ben7nthia7.n1-7-yI)-VTr, Using 4-methoxy-7-morpholin4-yl-benzotniazol-2-yl-arniQe and 2-memoxyethylamine the title compound was obtained as an off-white solid (80 %), MS: m/e = 367 (M+tF). Example 395 1 -(2-DimethylamTTin-etbyI1-3-f 4-methoxv-7-morpholin-4-yl-benzothiazol-2-yl")-1-methyl-urea Using 4-methoxy-7-moipholin4yl-benzolinazol-2-4yl-amiDe and WJOT-trimemylethylenediamine the title compound was obtained as an off-white solid (61 %), MS:m/e4394(M+H+). Example 396 1 - (2-Dimemyiaminn-rthyl)-3-f 4-methoxy-7-rofirphnlin -4-yi-ben2otbiazQl-2-yl)-urea Using 4-methoxy-7-morpholm-4-yl-benzothiazol-2-yl-arnine and 2-dimethylamino-ethyiamine the title compound was obtained as an off-white solid (79 %), MS: m/e = 380 (M+H1"). Following the general method of example 379 the compound of example 397 was prepared Example 397 4-DimrtkylaTTimf>-W-f4-memo;jqr-7-morpholm-4 Using 4-methoxy-7-morphoun-4-yl-benzotaiazol-2-yi-amine and 4-dimethyiammo-butyryl chloride the title compound was obtained as a light yellow solid (10 %), MS: m/e = 379 (M+fT): Preparation of intermediates for examples 1 to 187 Example 398 (7-Iodo-4-methoxy-benzotbiazol-2-ylVcarbamic acid methyl ester (4-Metlioxy-benzoiiuazol-2-yl)-carbaraic acid methyl ester (31.0 g, 130 mmol) and sodium acetate (32.3 g, 394 mmol) are dissolved in 400 ml of glacial acetic acid and slowly i treated with iodine monochloride (13.5 ml, 264 mmol) at 0 °C. The reaction rnixture is then slowly warmed to room temperature and stirred for 15 hours. After addition of water (131), the formed precipitate is filtered off and washed with water. The filter cake is then dissolved in a minimal amount of tetrahydroturane (about 150 ml) and decolorized with IM aqueous sodium rhiosulfate. The product is piecipltated by the addition of water (about 2.01), filtered off and dried at 60 °C for 12 hours. 423 g (89 %) white solid. MS: m/e= 364 (M+). Example 399 (4-Memo:xy-benzothiazol-2-yl)-carbamic acid methyl ester 2-Arnmo-4-methoxyberrzothiazol (23.6 g, 131 mmol) and pyridine (12.6 ml, 157 mmol) in dichloromethane (230 ml) are slowly treated with methyl chloroformate (10.6 ml, 137 mmol) at 0 °C. After 10 minutes, further methyl chloroformate (1.0 ml, 13 ramol) and pyridine (1.0 ml, 12 mmol) are added. After 10 minutes, the mixture is poured into 200 ml 1M aqueous hydrochloric arid, the organic layer is separated, diluted with dichloromethane (250 ml) and washed with brine (50 ml). The organic phase is dried and the solvent evaporated in vacuo. 31.0 g (99.4 %) white solid. MS: m/e= 238 (M+H). Example 400 f4-Memoxv-7-phenyl-4?eiizoyhiazol-2-yl)-carbamic acid tert-batvi ester To a suspension of 2-armno-4-memoxy-7-phenyi-benzothiazole (1.0 g, 3.9 mmol) in THF (50 ml) was added di(tert-butoxycarbonyl)-anhydride (BOC)20 and DMAP (47 mg, 0.04 mmol) and the mixture stirred for 1 h a r.L, followed by 3 h at 60 °C After cooling the solvent was evaporated and the residue chromatographed over SiOz (Merck 230-400 mesh) eluting with a gradient of cydohexane/EtOAc (10 % to 50 % EtOAc), after pooling the product fractons and evaporation of the solvents the title compound was obtained as a white foam (1.1 g, 79 % yield), MS: m/e=356 (M). Example 401 f4-Methoxy-benzothiazol-2-yl)~carbamif- acid tert-butyi ester Using 2-amino-4-mefhoxy-benzothiazole the title compound was obtained as a white solid (60 % yield), MS: m/e=281.2 (M+H). Example 402 2-Amino-4-methoxy-7-phenyl-benzotfaLazoIe The title compound was prepared from 3-ainmo-4-methoxy-biphenyi, according to the patent literature N~(Benzothiazol-2-yl)oxamic acid derivatives. W. Winter, M. Thiel, A. Roesch and O. H. Wflhelms, German Patent, DE 2656468,1978. and is obtained as a white solid, MS: m/e=256 (M), mp. 207-208 °C. Example 403 4-Memoxy-7-phejioxy-benzotfaiazol-2-yl-amine To a suspension of 2-memoxy-5-phenoxy-phenyi)-thiourea (8.25 g, 30 mmol) in CHO3 (70 ml) was added bromine (4.8 g, 30 mmol) in CHQ3 (10 ml) dropwise over 10 min. The mixture was then heated to reflux for 3 h, then cooled to r.t, the solvent was evaporated and the residue crystallised from MeOH/ether (1:4). The filter cake was then further washed with saturated aqueous NaHS03 solution /water (1:1), (100 ml), water (200 ml), IN NaOH (60 ml), then water (100 ml), and finally ether (100 ml). The solid material thus obtained was dried under vacuum (0.05 mmHg, 60 °C) to afford the tide compoud as a white solid (6.7 g, 82 % yield), MS: m/e=272.1 (M). Following the general method of example 403, the compounds of examples 404 to 409 were prepared Example 404 ?.-Amino-4-medioxy-benzothiazole-7-carboxYhc arid methyl ester Using 4-methoxy-3-thioureido-benzoic acid methyl ester the title compound was obtained as a white solid (55 % yield), MS: m/e=239.2 (M+H4). Example 405 7-Bromo-4-methoxy"benzothiazole-2-yl-aiTiinf Using (5-bromo-2-methoxy-phenyl)-thiourea the title compound was obtained as a white solid (46 % yield), MS: m/e=258 (M). Example 406 7-tert-Butyl-4-methoxy-benzothiazole-7--vl-aTTiinp Using (5-tert-butjd-2-metfaoxy-phenyl)-rhiourea the title compound was obtained as a white solid (79 % yield), MS: m/e= 238.1 (M). Example 407 7- Acetyjarmnn -4-methoxy-h«!"n74t4ia2oIe-2-vl-arninf Using (5-acelyIamino-2-methoxy-phenyl)-thiourea me title compound was obtamed as a purple solid (49 % yield), MS: m/e=238.2 (M+fT.) Example 408 4-methoxy-7-(" lH-tetrazoI-5-yI Vhen snthia7.pl-2-yj-amin4 Using 2-methoxy-5-(lH-tetrazol-5-yl)-phenyl]-thiourea die title compound was obtained as a tan solid (54 % yield), MS: m/e=248.2 (M) Example 409 f4-Methoxy-7-phenyi4?en2otHazol-2-yl)-methyl-arnine Jsing (4-medioxy-biphenyl-3-yl)-thiourea the title compound was obrtained as a white ;olid (71 % yield), MS: m/e=270.1 (M+). Example 410 5-Memoxy-7-phenyI-benzothiazoI-2-Yl-amin"e (5-Methoxy-biphenyl-3-yl)-thiourea (109 mg, 0.42 mmol) in chloroform (2 ml) are treated with bromine (22 ul) and the mixture heated to 61 °C for 5 hours. After removal of the volatile components in vacuo, the product (93 g, 86 %) is isolated by flash chromatography (silica, eluent ethyl acetate/cyclohexane 2:1 to 5:1) as beige solid. The regiochemistry of the cychzation was checked by transfer-NOE measurements. MS: m/e= 256 (M+). Example 411 ?.- Ami n ft4,5-dimethoxvbari20thiazol 2-Ammo-4,5-o!imetlioxybanzothiazol is synthesized starting from 2,3-dimethoxyaniline (1.0 g, 6.5 mmol) in the same manner as described for 5-memoxy-7-phenyl-benzothiazol-2-yl-amine in 72 % total yield over three steps. MS: m/e= 210 (M). Example 412 6-Bromo4trifluoromemoxy-benzothiazol-2-yl-arnTnfi 4-Bromo-2-irifluoromethoxy)aruline (768 nig* 3 mmol) and potassium thiocyanate (875 mg, 9 mmol) are dissolved in acetic acid (5 ml) and at 0 °C, bromine (0.19 ml, 3.6 mmol) are slowly added. After stirring for 1 h, acetic acid (2 ml) are added and the mixture heated to 100 °C for 3 h. After cooling to room temperature, aqueous sodium hydroxide (10M, 25 ml) is added and the mixture extracted three times with ethyl acetate. The combined organic layers were wasged with brine, dried and the solvent removed in vacuo. Hash chromatography (silica, eluent ethyl acetate/cydohexane 1:4) and final recrystaHization from ethyl acetate/cydohexane affords the product as white solid. 170 mg (18 %). MS: m/e= 315 (M+rT). Example 413 4-Memoxv-7-morpholm4-vl->w47r>r}iiazol-2-yl-amJne (2-Methoxy-5-morpholin-4-yl-phenyl)-thioiarea (5.0 g, 19 mmol) in chloroform (130 ml) are treated with bromine (960 ul) and the mixture retluxed for 18 hours. After removal of the volatile components in vacuo, the product is recrystallized from THF (2.8 g, 57 %). MS: m/e= 266 (M). Example 414 7- Benzylpxy -4-memoxy-benzothiazole-2-yl-amine Synthesized starting from (5-Benzvloxy-2-methoxy-phenyl)~thiourea in the same manner as described for 5-memoxy-7-phenyl-benzotbiazol-2-yl-amine in 82 % yield as a beige solid. Mp: 165 °C (dec). Example 415 4-Trifluoromethoxy-benzotlua7ol-2~yl-ariune 6-Bromo4lrifiujDrometb,oxy~ben2otlu4ol-2-ylamine (157 rag, 0.50 mg), triethylamine (0.21 ml, 1.5 mmol) and palladium on carbon (10 %, 15 mg) are suspended in ethanol (12 ml) and hydrogenated at atmospheric pressure for 96 h. The catalyst was filtered off and the solution evaporated to dryness. The residue was dissolved in ethyl acetate, washed three times with water, dried and the solvent removed in vacuo. The product is obtained as brown solid (85 mg, 73%). MS: m/e= 235 (M+H). Example 416 -Amrno-4-methQxy-benzothia2ole-7-carbaldehvde fsing (5-Fonnyi-2-methoxy-phenyI)-thiourea the title compound was syrithesised as escribed for 4-methoxy-7-phenoxy-benzotBia4I-2-yl-amine and obtained as a beige solid 70 % yield), MS: m/e=208.0 (M). Example 417 -Memoxy-7-morphoUn4Ymielhyl-berizotHa4 To a suspension of 2-amino-4-methoxy-ben20thiazole-7-carbaldehyde (440 mg, 2.1 nmol) in THF (100 ml) was added morpholine (276 mg, 3.2 mmol), acetic acid (190 mg, 5.2 mmol) followed by NaBH(OAc)3 (672 mg, 3.2 mmol). This mixture was stirred rigorously at 20 4C for 48 hours, after which time water (50 ml) and 5 % NaHC03 solution 450 ml) were added and the mixture agitated vigorously. After separating the organic and iqueous layers, the aqueous phase was extracted with EtOAc (50 ml) and the combined organic phase was washed with saturated Nad solution (100 ml) then dried with Na4SO, filtered and evaporated. The solid residue was suspended in ether (20 ml) and filtered then the filter cake was washed with ether (10 ml), and dried under vacuum (O.05 mmHg, 50 °C) to afford the title compound as a yellow solid (430 mg, 73 % yield), MS: m/e=280.2 Example 418 2-Chloro-4-methoxy-7-phenvl-benzothiazole To a suspension of 2-arnino-4~memoxy-7-paenyl-benzoliiiazole (5.1 g, 20 mmol) in ethylene glycol (75 ml) were added hydrazine monohydrate (4 g, 80 mmol) and hydrazine dihydrochloride (4.2 g, 40 mmol) and the suspension was heated for 18 h at 140 °C After cooling to r.L the suspension was filtered, then the filter cake was washed with water (200 ml) followed by ether (100 ml), and dried under vacuum (0.05 mmHg, 70 °C) to afford 2-hydrzmo-4-methosy-7-phenyl-ben2othiazole as a white solid (5.2 g, 96 % yield). The 2-hydjrzirio-4-memoxy-7-phenyl-ben2othiazole (4.5 g, 16.6 mmol) was then added in portions over 20 rain, to stirred neat thionyl chloride (12 ml, 165 mmol), the mixture was then heated to 50 °C for 2 h to complete the reaction. The reaction mixture was then cooled and poured on to ice/water (300 ml) and stirrd for 20 min. at 0-10 °C. The whole mixture was then filtered and the filter cake waas washed with water (100 ml). The filter mke wa? then dissulnulmCH4Q; (250 mi) and-washed wife wtttiatcdNgQaohrtwthThe organic phase was dried with Na4C4 filtered and evaporaterd to aflfbed a red oil which was chromatographed over SiC>2 (Merck 230-400 mesh) eluting with CrtCb- The product fractions were pooled and evaporated to afford the title compound as a brown solid (4.24 g, 93 % yield), MS: m/e=275.0 (M). lit: Synth. Commun., 1992,2769-80. Example 419 4-(Morpholine-4-sulfonyl)-benzoic acid To a solution of 4-(chlorosulfonyi)-benzoic acid (05 g, 22 mmol) in THF (20 ml) was added morpholine (0.434 ml, 5 mmol) dropwise over 5 min, and this mixture stirred at r.t.for 1 h. Water (50 ml) was then addedand the mixture agitated, the phases were separated and the aqueous phase extracted with EtOAc (2x50 ml). The combined organic phases were washed with satd. aq. NaCI solution, dried, filtered and evaporated. The residue was chromatographed over S1O2 (Merck 230-400 mesh) during with a CHG3/Cacetone +10 % HCO2H) (9:1), the product fractions were pooled, evaporated and dried in vacuo (0.05 mmHg, 50 °C) to afford the title compound as a beige solid (270 mg, 20 % yield), MS: m/e=s271 (M). Following the general method of example 419, the compounds of examples 420 to 422 were prepared Example 420 4-Dipropylsulfamovl-benzoic acid Using dipropyiamine the title compound was obtained as a beige solid, MS: m/e=285 (M)- Example 421 4-Ethylsulfamoyi-benzoic acid Using ethyiamine the title compound was obtained as a white solid (85 % yield), MS: m/e=228.1 (M-H)Example 422 tylsuhami Using diethyjamine me title compound was obtained as a white solid (44 % yield), MS: m/e=257 (M). Example 423 l-( 1,1 -Dioxo-tiuomorphohii-4-yIVethylamine The tifle compound was prepared according to the following patent literature: W. R, Baker, S. A. Boyd, A. K. L Fung, H. H Stein, J. F. Denissen, C. W. Hutchins and S. H. Rosenberg, WO 9203429 (1992). Example 424 MemyH4ffletfavl-pyridin-3-vlropitTiv1)-arninR To a suspension of liAlHt in THF (120 ml) at 10 °C was added a solution of methyl-6-methyl nicotiiiate (12 g, 79 mmol) in THF (80 ml) dropwise with cooling over 45 win. After stirring 1.5 h at 20 °C, a mixture of THF/water (4:1) 60 ml was added to the reaction over 30 min. at 0 °C, NazSC>4 (50 g) was then added dircuy to the reaction mixture which was stirred vigorously, then filtered and the THF evaporated in vacuo. The residue was chromatographed over S1O2 (Merck 230-400 mesh) eluting with a gradient of CHidj/MeOH (97:3 to 9:1), affording a colourless oil (7.5 g, 77 % yield). This material was dissolved in CHQ3 (100 ml) and treated dropwise with thionyl chloride (17.2 ml, 237 mmol) stirred at 5 °C to 20 °C over 16 h. The solvents were then removed in vacuo and the residue partitioned between CH2C2 (100 ml) and aq. 5% NaHCC>3 (100 ml), the aqueous phase was further extracted with CH2CI2 (2x 50 ml) and the combined extracts washed with satd. aq, NaCI solution (1x50 ml), then dried and the solvent evaporated in vacuo. The resulting red oil was dissolved in EtOH (80 ml) cooled to 0 °C and treated with 33% memyiamine /EtOH (50 ml) dropwise over 1 h, then the mixture was stirred to 20 °C over 3 h. After evaporation of all the solvents the residue was partitioned between CH2Q2 and water (100 ml ea.), the aqueous phase was further extracted with CH2G2 (2x 100 ml), dried (Na2S04), filtered and the solvent evaporated in vacuo. The brown oily residue was then distilled under high vacuum (0.1 mm Hg, 68-70 °C) over a Vigreux column to afford the title compound as a pale yellow liquid (6.03 g, 75 % yield), MS: m/e= 136.1 (M). Lit/. Med. Chem., 1996,5053-63. Following the general method of example 424, the compounds of examples 425 to 4266 were prepared Example 425 Methyl-pyridin-2-yl-mfithyt-ainin e Using 2-cHoromethyl-pyridine hydrochloride salt and 33 % methylamine/EtOH the title compound was obtained as a colourless liquid (0.1 mm Hg, 47-48 °C) (20 % yield), MS: m/e=93.1 (M-NHCH3). Example 426 Methyl-pyridin-4-vlniethyl -amine-. Using 4-chloromethyl-pyridine hydrochloride salt and 33 % methylamine/EtOH the title compound was obtained as a colourless liquid (0.1 mm Hg, 60-62 °C) (79 % yield), MS: m/e4I22.1 (M). Preparation of intermediates for examples 188 to 208 Example 427 2-Methoxy-5-phenoyy-plienyl)-thiourea To a solution of 2-methoxy-5-phenoxy-aniline (9.9 g, 46 tnmol) in acetone (60 ml) was added benzoylisothiocyanate (9 g, 55 mmol) and the mixture heated to reiux (56 °C) for 4 h. After cooling to r.t., the solvent was evaporated and the oily orange residue was precipitated from ether (20 ml) under ultrasonnication, the solid was then washed on the filter with ether/ nHexane (1:3) (50 ml). The solid thus obtained was further dried under vacuum (0.05 mmHg, 50 °C) to afford the benzoylated thiourea as a beige solid (17.2 g, 99 %, yield). Fresh sodium metkoxide (14.5 g, 38 mmol) was men added to a suspension of the benzoylated thiourea (14.5 g, 38 mmol) in methanol (70 ml) and this mixture stirred for 1 h at r.t. Water was then added (210 ml) and the precipitated solid was collected, then washed on the filter with water (100 ml), followed by ether (100 ml), then dried under vacuum (0.05 mmHg, 50 C) to afford the title compound as a white solid (8.5 g, 81 % yield), MS: m/e=274.1 (M). Following the general method of example 427 the compounds of examples 428 to 433 were prepared Example 428 (5-tert-Butyl-2-methoxv-phenvl)-thiourea Using 4-tert-buty!-2-methoxy-aniliQe the title compound was obtained as a white solid (79 % yield), MS: m/e=238.1 (M). Example 429 i"5-Acetviamino-2-methoxy-pheny])"thipurea Using 3-an2ino-4-metho2face£anilide the title compoimd was obtained aS a grey solid (69 % yield), MS: m/e= 240.3 (M+H). Example 430 4-Methoxy-3-thioureido-benzoic acid methyl ester Using 3-Amino-4-methoxy-benzoic acid methyl ester the title compound vras obtained as a tan solid (78 % yield), MS: m/e=240.0 (M+). Example 431 f5-Bromo-2-methosy-phen4)-diiourea Using 5-bromo-2-methoxy-aniline the title compound was obtained as a white solid (88 % yield), MS: m/e=260 (M). Example 432 2-methoxy-5-QH-tetrazol-5-yl)-phenyii-thiourea Using 2-methoxy-5-(lH-tetrazol-5-yl)-anuine the tide compound was obtained as a tan solid (92 % yield), MS: m/e=250.1 (M+). Exampl433 1 -f4-Metho:CT-biphen¥i-3-yl)-3-memYi-thiourea Using 4-methoxy-biphenyi-3-ykmine and N-methyi-isothiocyanate the title compound was directly obtained as a white solid (96 % yield), MS: m/e=273.2 (M+rT). Example434 (5-Methoxv-biphenyI-3-ylVuiioiirea l-Benzoyl-3-(5-methosy-biphenyl-3-yl)-thiourea (183 mg, 0.51 mmol) in methanol (5 ml) are treated with sodium methoxide (5.4M in methanol, 0.14 ml) and the formed pxecipitsle is Altered aflL Washing with p4hann? yifiirii >• pnaduct (115 iflfc4 %J as, oi£r white powder. MS: m/e= 258 (M). Example 435 1 -Benzovi-3- (5-methoxy-biphenvl-3-yi Vthioorea 5-Methoxy-biphenyl-3-ylamine (129 mg, 0.65 mmol) are dissolved in acetone (5 ml) and slowly treated with a solution of benzoyl isothiocyanate (0.096 ml, 0.71 mmol) in acetone (2 ml). After stirring at ambient temperature for 18 h, the solvent is removed in vacuo and the residue crystallized from hexane. The product (203 mg, 86 %) is obtained as colorless crystalk Mp 149 °C. Example 436 (2-Methoxv-5-morpho"in-4-yi-phenvl")-thiourea 1 -Benzoyi-3-(2-methoxy- 5- morpholin-4-yl-phenyl) -thiourea (8.0 g, 21 mmol), suspended in methanol (260 ml), are treated with 6 ml sodium methanolate (5.4M in methanol) and the mixture stirred until a white precipitate forms. The mixture is concentrated in vacuo, the crystals are isolated by filtration and washed with methanol and hexane (5.0 g 86 %). MS: m/e= 268(14). Example 437 l-Benzoyl-3-f2-memoxy-5-morpholin-4-vl-phenylVthiouTea To a solution of 2-methoxy-5-morphoIm-4-yI-phenyIamine (4.6 g, 22 mmol) in acetone (140 ml) is added a solution of benzoyl isithiocyanate (3.4 ml, 25 mmol) in acetone (80 ml) and the reaction mixture is stirred for further 30 min at ambient temperature. After removal of the volatile components in vacuo, the product is isolated by flash chromatography (silica, eluent ethyl acetate/n-hexane 1:4, then 1:2) as a yellow solid (8.0 g, 97 %). MS: m/e= 272 (M). Example 438 (5-BenzyJoxv-2-memoxy-phenvlV thiourea Synthesized from 5-benzyloxy-2-methoxy-aniline as described for example 427 in 80 % overall yield. Obtained as white crystals. M.p. 130 °C (dec.). Example 439 (5-Fomiy42-ipetiw)«v-4)bew4>-tiBottrea To a solution of 2-(4-methoxy-3-nitro-phenyl)-[13]dioxolane (13 g, 57.7 mmol) in MeOH (400 ml) was added Adams catalyst-Pt(02) (700 mg) and the mixture stirred vigorously under an atmosphere of hydrogen at 20 °C until 41 of hydrogen had been taken up. The catalyst was then filtered off and and methanol evaporated and replaced with acetone (150 ml). Benzoyl isothiocyanate was then added dropwse (8.5 ml, 63.5 mmol) over 15 min at r.Land the mixture then heated to reflux for 1.5 h. After cooling the solvent was evaporated and the residue was chromatographed over SiCh (Merck 230-400 mesh) eluting with CH2Q2 affording a yellow oil (10 g). This oil was teken up in MeOH (150 ml) and sodium methoxide was added (3.7 g, 69 mmol) and the mixture stirred at 20 °C for 1 h. Following this the solvent was evaporated and the residue dissolved in THF (200 ml) and 2N HO (100 ml) was added and the mixture stirred for 30 min. EtQAc (200 ml) was then added and the aqueous phase separated and extracted with EtOAc/THF (1:1) (200 ml). The combined organic phases were washed with satd. aq. NaCl solution (2x 200 ml), dried, filtered and the solvent evaporated. The solid residue was suspended in ether (100 ml) and filtered off, washed with emer (50 ml) and drid under vacuum (0.05 mmHg, 50 °C) to afford the title compound as a yellow solid (4.7 g, 39 % yield). MS: m/e=210.1 (M). Example 440 2-(4-Mel3ioxy-3-nitro-phenviV 1131 dioxolane To a solution of 4-methoxy-3-nito-ben2aldehyde (11.2 g, 61.8 mmol) in toluene (300 ml) was added ethylene glycol (5.2 ml, 92.7 mmol) and Amberlyst A15 resin acid catalyst (0.6 g). This mixture was stirred vigorously at reflux for 16 h. in a Dean-Stark apparatus. Upon cooling the Amberlyst resn was filtered off and the filtrate washed with satd. aq. Nad solution (3x150 ml), then dried with Na2SO, filtered and evaporated to aflbrd the title compound as an orange oil (14 g, 100 % yield), MS: m/e=224.1 (M-H)Example 441 2-Meihoxv-5-f lH-tetrazol-5-vlVaDilmp To a solution of 4-methoxy-3-nitro-benzonitrile (2.5 g> 1.4 mmol) in toluene (20 ml) was added sodium azide (1.3 g, 1.8 mmol) and triethylamine hydrochlride (1.5 g, 1.8 mmol), and this mixture stirred at 100 °C firo 48 h. Water was then added (200 ml) and the mixture ) agitated, the aqueous phase was further washed with water (2x30 ml). The organic phase was then adjusted to pH 2 and the solid which precipitated was filtered off and washed further with water (100 ml) then dried in vacuo (0-05 mmHg, 60 °C) to afford the crude tetrazole. This material was then directly dissolved in MeOH (80 ml), Pd/C (10%) (250 mg) was added and the mixture stirred under 1 atm of hydrogen at 20 °C for ca.1 h until the theoretical amount of hydrogen (ca. 880 ml) had been taken up. The catalyst was then filtered off and the solvent evaporated to afford the title compound as a white solid (2.2 g, 82 % yield), MS: m/e=191.1 (M). Lit Synthesis 1998, p910. Example 442 1 -Iodo-3-methoxy-5-nitro-benzene l-Iodo-3,5-dinitrobenzene (1.8 g, 6.1 mmol) are dissolved in methanol (12 ml) and treated with a solution of sodium methoxide in methanol (5.4M, 1.2 ml). The mixture is then stirred at 65°C for 52 h. After cooling to ambient temperature, water (50 ml) is added and the mixture extracted three times with ethyl acetate (50 ml). The combined organic layers are extracted with brine (100 ml), dried and evaporated to dryness. Hash chromatography (silica, eluent ethyi acetate/cydohexane 1:1) affords the product (1.7 g, 99%) as light yellow solid. MS: m/e= 279 (M). Example 443 S-Methoxy-biphepyl - Vyl-armTip 3-Methoxy-5-nitro-biphenyl (176 mg, 0.77 mmol) are hydrogenated in ethanol (5 ml) using palladium on carbon (20%, 17 mg) at atmospheric pressure for 2h, The caklyst is filtered off and the solvent removed in vacuo. Flash chromatography (silica, eluent ethyl acetate/cydohexane 1:1) affords the product (139 mg, 91 %) as a bown oil. MS: m/e= 199 (M+). Example 444 2-Memoxv-5-morpholin-4-vl-phpny1amiTie 4-(4-Methoxy-3-nitro-phenyl)-morpholine (6 g) is hydrogenated in dichloromethane (100 ml) and methanol (600 ml) using palladium on carbon (10 %,600 mg) for 12 hours. The catalyst is removed by filtration and the solution evaporated in vacuo. Purification by flash chromatography (silica, eluent ethyl acetate/n-hexane 1:1, then ) affords the product as off-white solid (4.6 g, 88 %). MS: m/e= 209 (M+H+). Example 445 4-f4-Methoxv-3-nitro-phenyD-morpholine 4-Bromo-2-nitroanisol (8.5 g, 36 mmol)> morpholine (3.8 ml, 44 mmol), potassium phosphate (11 g, 51 mmol), 2-biphenvI-dicyclohexyl phosphine (960 mg, 2.7 mmol) and palladium(n)acetate (411 mg, 1.8 mmol) are dissolved in dimethoxyethane (80 ml) and stirred at 80 °C for 96 hours. The mixture is then cooled to room temperature, diluted with ethyl acetate (50 ml) and filtrated through dicalite. Flash chromatography on. silica (eluent dichloromethane/methanol 99:1) affords the product as red solid (6.0 g, 69 %). MS: m/e= 238 (M+). Example 446 3-Methoxy-5-nitro-biphenyl l-Iodo-3-methoxy-5-nitro-benzene (279 mg, 1 mmol), phenyiboronic acid (146 mg, 1.2 mmol), potassium carbonate (2M, 1.0 ml) and tetrakis(triphenvlphosplnho)palladium(0) are dissolved in ethanol (0.5 ml) and toluene (10 ml) and the mixture heated to 90 °C for 24 h. The volatile components are removed in vacuo and the residue codistiUed twice with toluene. Flash chromatography (silica, eluent dttchloromethane/cyclohexane 1:2) affords the product (185 mg, 81 %) as light brown solid. MS: m/e= 229 (M1"). Example 447 5-Bromo-2-methox7-aniline A solution of 4-bromo-2-ni£ro-anisole (7.7 g, 33.1 mmol), triethylamrae (4.6 ml, 33.1 mmol) and Raney Nickel catalyst (4 g) was vigorously stirred in ethanol (30Q ml) under an atmosphere of hydrogen for 1 h at 20 °C. After this time the theoretical amount of hydrogen had been absorbed (2.51), so the catalyst was filtered off and the solvent evaporated to afford the title compound as a light yellow solid (7 g, 104 % yield), MS: m/e= 201 (M). intermediates for the preparation of benzvlic amines Example 448 4-Chloromethyl-N-f4-hydroxv-7-morpholm4yl-bei4omiazol-2-yl)-benzarniHf" N-(4-Benzyloxy-7-morpholin4yl-ben20thiazol-2-yl)4chloromemyl-benzaniide (1.0 g, 2-Q mmol) were, dissolved uiCHaCla (10 ml) andtreated.at-78. °CwiIhtetrabutyi ammonium iodide (0.95 g, 2.6 mmol) and a solution of boron trichloride in CH2U2 (.IM, 7.4 ml). After subsequent warming to 0° and stirring for additional 2 h, ice (2 g) and then water (10 ml) and methanol (2 ml) were added and the phases separated. The aqueous phases were extracted twice with CHjQj/MeOH, the combined organic layers "were dried with Na2S04 and evaporated to dryness. Recrystallization from CHjCfe/MeOH afforded the title compound as an off-white solid (18 %). MS: m/e= 403 ([M-H]"). Example 449 4-fl-Bromo-emvl)-N-(4-me&o4-7-morpholm4yl-te Following the general method of example 1 the title compound was obtained as a yellow solid (63 %). MS: m/e= 478 (M+rT). Example 450 3-ChloromethvI-N"(4-memoxy-7-morphoh44yl-benzothiazol-2-ylVben?.arniflp Following the general method of example 1 the title compound was obtained as a light yellow solid (59 %). MS: m/e= 418 (M+H). Example 451 4-Chloromemyi-3-fiuoro-N-(4-methoxy-7-morpholm4vI-benzotrn4ol-2-4Vbenzamide Following the general method of example 1 the title compound was obtained as a light brown solid (99 %). US: m/e= 436 (M+H). Example 452 4-Chioro-3-chIoromemyi-N-(4-methoxy-7-morpholm4 Following the general method of example 1 the title compound was obtained only in 75% purity (68 %) and used in the subsequent steps without further purification. MS: m/e= 452 (M+FT). Example 453 4-ff2-Methoxy-ethYl)-methvl-sulfamoyn-ben2oicacid 4-Chioro-suIfonyl-benzoic acid (100 mg, 0.45 mmol) were dissolved in (2-methoxy-ethyI)-methyl-amine (1.0 g, 11.2 mmol) and heated to 50 °C for 18 h. Removal of the volatile components in vacuo and flash chromatography (silica, ement C4CyMeOH/FkO/AcOH 90:10:1:1) afforded the product as white solid (65 %). MS: m/e= 272 ([M-H]")- ftniwmerfTflteg fui trie pieyiaiaftomTrl)ffii/yTTi_aniinesfer54-OBg? Example 454 4-Benzvloxv-7-moiphou44)d-benzolhia2ol-2-yi-amine Using 2-benzyloxy-5-morpholm-4-yl-phenyl)-tbiourea following the general method of example 403 the title compound was obtained as off-white solid (69 %). MS: m/e= 342 (M+H). Example 455 N-f4-Benz4oxv-7-morpholin-4-)d-benzoimazol-24-4-cMorometfa4-bpn7.arTiiHf; Following the general method of example 1 the title compound was obtained as a pale yellow solid (81 %). MS: m/e= 494 (M+H+). intermediates for the preparation of benzync amines for changed 7-position: Example 456 4-Memoxv-7-thiomorpholm-4-yl-benzotma2ol-2-yl-amuie Using 2-methoxy-5-thiomorpholin-4-yl-phenyi)-tbiourea following the general method of example 403 the title compound was obtained as light brown solid (31 %). MS: m/e= 282 (M+H). Example 457 f4-Methoxv-7-l"2-methvi-pyridm-4Yl)-hf"Ti7nfhia7ol-2-Yli-carbarm"c add methvl ester Using the general procedure B the title compound was prepared from 4-methoxy-7-morpholin-4-)d-benzothiazol-2-4-aniine and 2-meth}4-4-rrimetbylstannanyl-pyridine as a white solid (8%). MS: m/e= 329 (M). Example 458 4-Memo4-7-(2-methv1-pyridm4-ylVbenzothiazo]-2-4-amine [4-Memoxy-7-(2-methyl-pyridm4yl)-benzotmazol-2-yl]-caibarmc add methyl ester (100 mg, 0.24 mmol) were dissolved in ethyleneglycol (3.0 ml) and treated with potassium hydroxide (528 mg, 1.1 mmol) and heated to 100 °C for 6.5 h. The reaction mixture was cooled to room temperature, diluted with water, neutralized with IN HQ and extracted four times with ethyl acetate. The organic layers were combined and washed with water and saturated aqueous Nad. The organic phases were then dried and the solvent removed in vacuo. The product was obtained as a light brown solid (83 %). MS: m/e= 272 (M+H1"). wherein R1 is hydrogen, Q-s-alkyl, Ci-6-aIkoxy, benzyloxy, cydoalkyioxy, halogen, hydroxy or trifluoromethyloxy; R3 is hydrogen, halogen, (Ve-aJkyJ or Ci. R4 is hydrogen, C^-alkyi, C2-6-aUcenyl, halogen, -C(O)- Ci. R" is (a) phenyl, substituted by halogen-Q_e-a]kyl, O(0)H or by the following groups -fCH2)n-C(0)-N(Rs)-(CH2>„ C^-alkoxy, -CCH3)nO-halogen- C^-alky], -(CH^O-fC^^O-Cr^kyl, -S(0)2-N(R!)-(CHAO- Ci-6-alkyl, -(CH2)nOR3, with the exception of OCHjandOH, KCH2)nN(R5KCH2)0-Cl.(5-alkoxy, -(CH^NfCCH^- C^-alkoxy]z, -(CH2)nNfS(0)2CH3]2, "(CH2)nN[R5J[SCO)2CH3J, -(CH2)nN(R> Cz-e-atayl, -{CH2)nN{R5)-(CH2)0-cycIoaIkjrl, -(CH2)nN(R5)-C(0)0- d-s-alkyl, -(CH^NC^MCHzk-S- Q.fi-alfcyl, -(CH2)aN(R5)-S(0)2CH5 -(CH2)aN(Rs)-(CH2)D-phenyl, -(CH2)»N(Hs)-(CH2)oOH, -{CHi)nN{R3)-(CH2)oCH(OH)-CF3! -(CH2)nN(R5)-(CH2)0-CF3> -(CH2)DNCRs)-CCH:)0-O-CH(OH)-CsH3(OCH3)2, -(CHaJnNCR^-CCH^o-O-aO-QHaCOCHa)!, -N(R5)-C(0)-morpholin> - N(R5)-C(0)-N(R5)-phenyl, substituted by Ci^alkcacy, -SCO 7-morpholin, or is phenyl, which is substituted by -(CR5R6)D-five to seven membered aromatic Or non aromatic heterocyde, and wherein the heterocyde may further substituted by hydroxy, -N(R5)(R6)orCj^-aIikyl; X is 0 or S; R5, R6are independently from each other hydrogen or Ci^-alkyl, R7 is d^alkyl, Cj^-alkoxy, -C(O)- Cus-alkyl, -C(0)Q-benzyI, -C(0)0- Ci-s-alkyl, - (CH2)nNR5R,s, pyridinyl, optionally substituted by Ci-s-alkyl, or is -CH2N(R5)-C(0)0-C1.s-aikyl, -NH-C(phenyI)3, pyrmlidinyl, piperidinyl, morpholinyl or piperazinyl, optionally substituted by Cj-s-alkyl; n is 0,1,2,3 or 4; m isOorl; o is 0,1, 2, 3 or 4; and their pharmaceutically acceptable salts, Some minor subgroups of compounds of the present formula I are known compounds and have been described, for example in EP 427 963, US 5,099,021, EP 295 656 or DE19 53149. These compounds possess microbicide activity or may be used for lowering the blood glucose level Furthermore, WO 00/18767 describes 2-piperazino alkylamino benzoazole, having an affinity to the dopamine subtype specific Bgands and are therefore useful in the treatment of diseases, related to this receptor. The compounds of WO 00/18767 are not encompassed from the scope of the present invention. It has surprisingly been found that the compounds of general formula. I are adenosine receptor ligands. Adenosine modulates a wide range of physiological functions by interacting with specific cell surface receptors. The potential of adenosine receptors as drug targets was first reviewed in 1982. Adenosine is related both structurally and metabolically to die bioactive nucleotides adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and cyclic adenosine monophosphate (cAMP); to the biochemical methylating agent S-adenosyi-L-methione (SAM); and structurally to the coenzymes NAD, FAD and coenzym A; and to RNA. Together adenosine and these related compounds are important in the regulation of many aspects of cellular metabolism and in the modulation of different central nervous system activities. The receptores for adenosine have been classified as Ai, A2A> A2B and A3 receptors, belonging to the family of G protein-coupled receptors. Activation of adenosine receptors by adenosine initiates signal transduction mechanism. These mechanisms are dependent on the receptor associated G protein. Each of the adenosine receptor subtyps has been classically characterised by the adenylate cyclase effector system, which utilises cAMP as a second messenger. The Ai and A3 receptors, coupled with Gj proteins inhibit adenylate cyclase, leading to a decrease in cellular cAMP levels, while A2A and AJB receptors couple to Gs proteins and activate adenylate cyclase, leading to an increase in cellular cAMP levels. It is known that the Aj receptor system include the activation of phospholipase C and modulation of both potassium and calcium ion channels. The A3 subtype, in addition to its association with adenylate cyclase, also stimulates phospholipase C and so Activates calcium ion channels. The Aj receptor (326-328 amino acids) was cloned from various species (canine, human iai* dog, ducl^bcivuie* guinear^rig) witiL9G^5& sequence identify amonftthe mammalian species. The AJA receptor (409-412 amino acids) was cloned from canine, rat, human, guinea pig and mouse. The A^ receptor (332 amino acids) was cloned from human and mouse with 45% homology of human A2B with human Ai and A2A receptors. The A3 receptor (317-320 amino acids) was cloned from human, rat, dog, rabbit and sheep. The Ai and A2A receptor subtypes are proposed to play complementary roles in adenosine"s regulation of the energy supply. Adenosine, which is a metabolic product of ATP, diffuses from the cell and acts locally to activate adenosine receptors to decrease the oxygen demand (Ai) or increase the oxygen supply (A2A) and so reinstate the balance of energy supply, demand within the tissue. The actions of both subtyps is to increase the amount of available oxygen to tissue and to protect cells against damage caused by a short term imbalance of oxygen. One of the important functions of endogenous adenosine is preventing damage during traumas such as hypoxia, ischaemia, hypotension and seizure activity. Furthermore, it is known that the binding of the adenosine receptor agonist to mast cells expressing the rat A3 receptor resulted in increased inositol triphosphate and intracellular calcium concentrations, which potentiated antigen induced secretion of inflammatory mediators. Therefore, the A3 receptor plays a role in mediating asthmatic attacks and other allergic responses. Adenosine is also a neuromodulator, possessing global importance in the modulation of molecular mechanisms underlying many aspects of physiological brain function by mediating central inhibitory effects. An increase in neurotransmitter release follows traumas such as hypoxia, ischaemia and seizures. These neurotransmitters are ultimately responsible for neural degeneration and neural death, which causes brain damage or death of the individual. The adenosine Ai agonists which mimic the central inhibitory effects of adenosine may therefore be useful as neuroprotective agents. Adenosine has been proposed as an endogenous anticonvulsant agent, inhibiting ghitamate release from excitory neurons and inhibiting neuronal firing. Adenosine agonists therefore may be used as antiepHeptic agents. Adenosine antagonists stimulate the activity of the CNS and have proven to be effective as cognition enhancers. Selective Aa,- antagonists have therapeutic potential in the treatment of various forms of dementia, for example in Alzheimer"s disease and are useful as neuroprotective agents. Adenosine A^- receptor antagonists inhibit the release of dopamine from central synaptic terminals and stimulate locomotor activity and consequently improve Parkinsonian symptoms. The central activities of adenosine are also implicated in the molecular mechanism underlying sedation, hypnosis, schizophrenia, anxiety, pain, respiration, depression and substance abuse. Drugs acting at adenosine receptors therefore have therapeutic potential as sedatives, muscle relaxants, antipsychotics, anxiolytics, analgesics, respiratory stimulants and antidepressants, and they may be used in the treatment of ADHD (attention deficit hyper-activity disorder). An important role for adenosine in the cardiovascular system is as a cardioprotective agent Levels of endogenous adenosine increase in response to ischaemia and hypoxia, and protect cardiac tissue during and after trauma (preconditioning). Adenosine agonists thus have potential as cardioprotective agents. Adenosine modulates many aspects of renal function, including renin release, glomerular filtration rate and renal blood flow. Compounds, which antagonise the renal affects of adenosine, have potential as renal protective agents. Furthermore, adenosine A3 and/or A2B antagonists may be useful in the treatment of asthma and other allergic responsesor and in the rxeament of diabetes mellitus and obesity. Numerous documents describe the current knowledge on adenosine receptors, for example the following publications: Bioorganic & Medicinal Chemistry, 6, (1998), 619-641, Bioorganic & Medicinal Chemistry, 6, (1998), 707-719, J. Med. Chem., (1998), 41,2835-2845, J. Med. Chem., (1998), 41,3186-3201, J. Med. Chem., (1998), 41,2126-2133, J. Med. Chem., (1999), 42, 706-721, J. Med. Chem., (1996), 39,1164-1171, Arch. Pharm. Med. Chem., 332,39-41, (1999). Objects of the present invention is the use of compounds of formula I and their pharmaceutically acceptable salts for the manufacture of medicaments for the treatment of diseases, related to the adenosine A2 receptor, novel compounds of formula I-A per se, their manufacture, medicaments based on a compound in accordance with the invention and their production as well as die use of compounds of formula I in the control or prevention of illnesses based on the modulation of the adenosine system, such as Alzheimer"s disease, Parkinson"s disease, neuroprotection, schizophrenia, anxiety, pain, respiration deficits, depression, asthma, allergic responses, hypoxia, ischaemia, seizure and substance abuse. Furthermore, compounds of the present invention may be useful as sedatives, muscle relaxants, antipsychotics, antiepileptics, anticonvulsants and cardiaprotective agents. The most preferred indications in accordance with the present jnwntjf>n ar** hn»T milifit Kacg nn the- A^ rtf Apfnr antstgcmicrir a^ti^ty a^ ^ lisorders of the central nervous system, for example the treatment or prevention of certain lepressive disorders, neuroprotection and Parkinson"s disease as well as ADHD and liabetes mellitus. The present invention relates also to novel compounds of the general formula wherein R.1 is hydrogen, lower alkyl, lower alkoxy, benzyloxy, cydoalkyloxy, halogen, hydroxy or trifiuoromethyloxy; R2, R3 are independently from each other hydrogen, halogen, lower alkyl or lower alkyloxy; R4 is hydrogen, lower alkyl, lower aDcenyl, halogen, -C(0)-lower alkyk -C(0)-halogen-lower alkyl, -CH(OH)-halogen-lower alkyl, -C(0)0-lower aDcyl, -NHC(0)-lower alkyl, -(CH2)n-OH, or is phenyl, which is optionally attached to the benzo group via the linker ~(0)m-(CH2)a- and is optionally substituted by N(R5)(R6), halogen or nitro, or is 2,3-dihydro-lH-indolyl, azepan-1-yl, [l,4]oxazepan-4-yl, or is a five or six membered aromatic or non aromatic heterocyde, which may be attached to the benzo group via the linker -(0)m-(CH2)„ or -N=C(CH3)- and is optionally substituted by one or two group(s) R7, wherein R7 is defined below; R" is (a) phenyl, optionally substituted by halogen-lower alkyl, -C(0)H or by the following groups -(CH2)n-C(0)-N(R5)-(CH2)nlower alkoxy, -(CH2)nO-halogen-lower alkyl, -(CH2)nO-(CH2)n+iO-lower aDcyl, -S(O)2-N(R5)-(CH2)r0-Iower aDcyl, -(CH2)D0RS, -CCH2)i.N(R5)-(CH2)0-lower alkoxy, -(CH2)nN[(CH2)0-lower aDcoxy]2, -(CH2)nN[S(0)2GH3]2, -CCH2)nK[R5jrsCO)2CH3], -(CH2)nN(Rs)-lower alkenyl, -(CH2)nN(R5)-(CH2)o-cycIoaIkyl, -(CH2)nN(R5)-C(0)0-lower alkyi, -(CH^-S-fCHbVNfR^R6), -(CH2)nN(R5)-(CH2)0-S-lower alkyi, -(CH2)nN(R5)-S(0)2CH3 -(CH2)amR5)-(CH2)0~phenji, -(CH2)nN(R5)-(CH2)oOH, -(CH2)nN(R5)-(CH2)0CH(OH)-CF3j -CCH2)nN(R5)-(CH2)0-CF3, -(CH2)DN(R5)-(CH2)O-0-CH(0H)-C6H3(0CH3)2J -CCH2)nN(R5)-(CH2)o-0-C(0)-QH3(OCH3)2j -N(R5)-C(0)-morpholin, -N(R5)-C(0)-N(R5)-phenyi, substituted by alkoxy, -S(0)2-morpholin, or is phenyl, which is optionally substituted by -(CR^Vfiveto seven membered aromatic or non aromatic heterocycle, and wherein the heterocycle may further substituted by hydroxy, -N(R5)(R6) or lower alkyi, or by -(CH2)nN{R5){CH2)0-nve or six membered aromatic or non aromatic heterocycle and wherein the heterocycle may further substituted by hydroxy, -N(R5)(R6) or lower alkyi, or is -N(R5)-phenyl, which is optionally substituted by lower alkoxy, or is b) -{CH2)n-five or six membered aromatic or non aromatic heterocycle, with the exception of the the piperazinyi group in case if n=0, which rings may be optionally substituted by 2-oxo-pyrrolidin, piperidinyl, phenyl, -(CH2)nOH, halogen, CF3, =0, lower alkyi, cydoalkyi, -(CH2)n-0-lower alkyi, -(CH2)„NH2, -(CH2)nCN, -C(O)0-lower alkyi, -CH2-0-S(0)2CH3> -C(0)-lower alkyi, -C(0)-(CH2)c-lower alkoxy, -CHj-NfR^QHiF, -CH2-N(R6)C(0)O-lower alkyi, -N(R6)-C(O)-N(R5)-(CH2)n-0-lower alkyi, -orby tetrahydrofuran, Substituted by 4-Q-phenyl, orbypipera2m-l-yl,morpholmyl,thiomorphoIinyI, thiomorpholin- 1-oxo, pyrroUdin-1-yl or by piperidin-1-yl or is benzopiperidin-1-yi or benzothien-2-yi, or c) -N(R5)(CH2)n+i-phenyl, optionally substituted by lower alkoxy, -0(CH2)n-phenyl, or -N(R5)C(0)-phenyi, or is d) -N(R5)(CH2)n-5-or 6 membered aromatic or non aromatic heterocycle, optionally substituted by lower alkyi, -(CH2)n-5-or 6 membered aromatic or non aromatic heterocycle oris e) -0-(CH2)a-lower alkoxy, lower alkyl-iower alkoxy, -NtR^CH^BNfRW), -(CH2)nOH, -(HC=CH)nC(0)0-Iower alkyi, octahydro-quinoline, 3,4-dihydro-lH-isoquinoline, 2^-ben2o-l,4-dioxa-8-a2a-spiro[4>5]decane or 1,4-dioxa-8-aza^spiro [4,5] decane. X is O, S or two hydrogen atoms; R5, R6 are independently from each other hydrogen or lower alkyi, R7 is lower alkyi, lower alkoxy, -C(0)-lower alkyi, -C(O)0-benzyl, -C(0)0-lower alkyl, -(CHjJnNR^6, pyridinyl, optionally substituted by lower alkyl, or is -CH2N(R5)-C(0)0-lower alkyl, -NH-C(phenyi)3, pyrrolidinyl, piperidinyl, morpholinyi, piperazinyl, optionally substituted by lower alkyl; n is 0,1,2,3 or 4; m is 0 or 1; o isO, 1,2,3 or 4; and to their pharmaceutically acceptable salts for the manufacture of medicaments for the treatment of diseases related to the adenosine receptor. As used herein, the term "lower alkyl" denotes a saturated straight- or branched-chain alkyl group containing from 1 to 6 carbon atoms, for example, methyl, ethyl, propyl, isopropyl, n-butyl, i-butyl, 2-butyl, t-butyl and the like. Preferred lower alkyl groups are groups with 1-4 carbon atoms. As used herein, the tqxm "lower alkenyT denotes a nn.^tnrat^ straight- or branched-chain alkyl group containing from 2 to 6 carbon atoms, for example, ethylerj, propyien, isopropylen, n-butyien, i-butylen, 2-butylen, t-butylen and the like. Preferred lower alkyl groups are groups with 2-4 carbon atoms. The term "cycloalkyl" denotes a saturated carbocydic group, containing 3-6 carbon atoms. The term "halogen" denotes chlorine, iodine, fluorine and bromine. The term "lower alkoxy" denotes a group wherein the alkyl residues is as defined above, and which is attached via an oxygen atom. The term "five or six membered aromatic or non aromatic heterocycle" denotes the following group: aromatic heterocyclic groups are, for example pyrrol-1-yl, tetrazolyl, imidazol-1 or 2-yl, pyrazoU-yl, pyridin-1,2,3 or 4-yl, pyrazinyl, pyrimidinyl, pyridazinyi, isothiazolyi, isoxazolyl, thiazolyl, thienyl or furyl; Non aromatic heterocyclic groups are, for example, pyrrolidinyi, imidazolidinyl, pyrazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyi, ttaomorpholin-l,l-dioxo or thiomorpholin-l-oxo. The term "phannaceua"cally acceptable acid addition salts" embraces salts with inorganic and organic acids, such as hydrochloric acid, nitric acid, sulfuric acid, phosphoric acid, citric acid, formic acid, fumaric acid, maleic acid, acetic acid, succinic acid, tartaric acid, methane-sulfonic acid, p-toluenesulfonic acid and the like. Preferred compounds of formula I are those, wherein R1 is methoxy, X is oxygen and R2/R3 are hydrogen. Exemplary preferred are compounds of formula I for the above mentioned use, wherein R is an unsubstituted or substituted five or six membered aromatic heterocycle, for example the following compounds: N-(4-methoxy-7-morpholm-4-yl-benzothiazol-2-yl)-2^ 5-methvl-tbiophene-2-carboxylic acid (4-methoxy-7-phenyl-ben2omiazol-2-yI)-amideJ 5-methyl-furan-2-carboxylic acid (4-memoxy-7-phenyl-ben2ofhiazol-2-yl)-amide) N-(4-memoxy-7-phenyl-benzotlnizol-2-yl)-isomcotinamide, 5-methyi-thiophene-2-carboxyiic acid (4-methoxy-7-pyridin-4-yl-benzomia2ol-2-yi)- amide, 5-memyl-thiophene-2-carboxylic acid (4-memoxy-7-pyridm-3-yl-benzothiazol-2-yl)- amide, 5-methyl-thiophene-2-carboxylic acid [4-methoxy-7-(2-methyl-pyridin-4-yl)- benzothia2ol-2-yl] -amide, ^mrihyA^kif«-ith«^-3^a»twgylif- VYJ [7-(^-a"»Ty>-ph*yi) \ mfthrtigy hf»i«vt"hiaTf\l-?. yi]-amide, N-(4-methoxy-7-l^ophen-2-)d-benzotiua2ol-2-yl)-2-methyl-isoiucotinamide> N- [4-methoxy- 7-(2-pyridin-2-j4-t]iiazol-4-)d)-beiizothia2ol-2-yi]-2-meth)4- isonicotinamide, N-[4-inethoxy-7-(2-pyiToiidin-I -yi-tbiazol-4-yi)-benzothiazo]-2-yl] -2 -methyl- isonicotinamide, N-{4-methoxy- 7- [2-(4-methyI-piperaziri-1 -yi)-thiazol-4-y] J-benzotiia2oJ-2-yi}-2-metbyi-isonicotinamide and N-[4-metiioxy-7-(5-metb)i-tHopb£n-2-^)-benzotbiazol-2-yI]-2-me&^-isordcotin 276 Further preferred compounds of formula I for the above mentioned use are compounds, wherein R is an unsubstituted or substituted five or six membered non aromatic heterocyde, for example the following compounds: morphoIine-4--carboxyUc add (4-memoxy-7-phenyl-benzotbiazol-2-yl)-amide, thiomorpholine-4-carboxylic add (4-memoxy-7-phenvl-ben2»thiazol-2-yl)-amide, 1-oxo-ll 4-thiomorpholine-4-carboxyhc add (4-methoxy-7-phenyl-benzothiazoI-2-yl)- amide, morpholine-4-carboxyHc add {4-memoxy-7-[2-(6-methyl-pyridm-3-7l)-thiazol-4-yi]- benzothia2ol-2-yl}-aiiiide> morphoIine-4-carboxyhc add [4-methoxy-7-(2-p)^dm-2-yl-diiazol-4-yl)-benzothiazol-2- yl]-amide, morpholine-4-carboxyhc add {4-methoxy-7-[2-(4-metiiyI-prpera2m-l-yl)-thiazol-4-yl]- benzothiazol-2-yi}-amide, morpholine-4-carboxyIic add [4-methoxy-7-C2-piperidm-l-yl-thiazol^yl)-berizothia2ol- 2-yl} -amide, morpholine-4-carboxyiic add [4-methoxy-7-(5-methyi-tbiophen-2-yl)-benzothiazol-2- yl]-amide, 4-(4-methco^-7-morphoIm-4-yl-beiizothia2»l-2-^ acid tert-butyl ester, l-acetyl-piperidme-4-carboxylic add (4-methoxy-7-morpholm-4-yl-benzotbiazol-2-yl)-- amide, 4-oxo-piperidine-l-carboxykc acid (4-methoxy-7-morpb.olin-4-yl-benzouiiazol-2-yl)- amideand l-oxo-l>.4-thiomorpholine-4-carboxyuc add (4-memoxy-7-piperidin-l-yl-benzothiazol-• 2-yl>-aimde. Preferred are further compounds, wherein R is methoxy, for example the following compounds: rac-[7-(2-bromo-l-hydroxy-ethyI)-4-memoxy-ben2ouiiazoI-2-yIJ-caTbaniic acid methyl ester, {4-metho:xy-7-[2-(6-mefhyl-pyria^-3-yl)-thia^ methyl ester, [4-methoxy-7-(2-pyridm-2-yl-thiazoM-yl)-b^ [4-methoxy-7-(2-piperidm-l-yl-tm"azol^-yl)-benzothiazol-2-yl]-carbamk acid methyl ester and {4-methoxy-7- [2-(4-methyl-piperazin- l-yl)-diiazol-4-yl] -ben20thiazol-2-yl}-carbamic acid methyl ester. Preferred compounds of formula I for the above mentioned use are those, wherein R is phenyl, optionally substituted by halogen, CF3, -CH2OH, -CH2NHCH2CH2OCH3> -CH2NHCH2CH2OH, -CH2NHCH2-pyridinyl> -CH2NH2, -CH2NHCH2CH2SCH3j -CH2N(CH3)CH2CH2SCH3,-CH2N(CH3)CH2CH2OCH3, -CH3N(CH2 CH3)CH2CH2OCH3, -CH2NHCH3, -CH2SCH2CH2N(CH3)2, -Cf^OCHs, -CH2OCH2CH20CH3 or -CH2N(CH3)C(0)OCH3, for example the following compounds: 4-hydroxymetiiyl-N-C4-memoxy-7-phenyl-benzotHa2oI-2-yI)-benzarnide, 4-fluoro-N-(4-methoxy-7-phenyl-benzothiazol-2-yi)-ben2amides 2-{4-fluoro-benzoylanmio)-4-methoxy-benzotfuazole-7-carboxylic add methyl ester, 4- [ (2-memoxy-^thylarnmo)-methyl] -N-(4-methoxy-7-phenyl-benzothiazol-2-yl)-benzamide, 4-[(2-hydroxy-emylammo)-methyl]~N-(4-methoxy-7-phenyl-benzotfaiazoI-2--yl)-benzamide, N-(4-melho:xy-7-phenyl-benzothiazol-2-yl)^{[(p benzamide, N-(4-methoxy-7-pherryl-benzotluarol-2-yl)^{[te benzamide, 4-arm^ome^yl-N-C4-methoxy-7-phenyI-benz»thiazoI-2-yiJ-berizamide, N-(4-metiioxy-7-phenyl-benzothiazol-2-yl) -4- [(2-memylsul£myl-ethylamrno)-metbyl] -benzamide, 4-{^2-memoxy-^thyl)-memyl-anrmo]-metnyl}-N-(4-methoxy-7-morphoh^ benzothiazol-2-yl)-benzamide, N- [7-(2-arnino-thiazol-4--yl) -4-metrioxy-benzodiiazol-2-yl]-4-fluoro-ben2amide, 4-fluoro-N-{4-methoxy-7- [2-(6^memyl-pyridin-3-yl)-thiazol-4-yl] -benzothiazol-2-yl}- benzamide, 4-fiuoro-N-(4-methoxy-7-tbiophen-2-yi-benzothiazol-2-yi)-ben2aiiiide, 4-fluoro-N-{4-methoxy-7- [2-(4-methyl-piperazin-l -yO-thiazol-4-yl] -benzothiazol-2-yI}- benzamide, 4-{[(2-methox7-etii^)-metii)d-amino]-meth7l}-N-{4-methoxj"-7-[2-(6-mefli^-pyridin-3- yi)-thiazol-4-^] -benzotbiazol-2-5d}-benzamide, 4-{[(2-Methory-^yl)-methyl-ainino]-met^ benzothiazol-2-ji)-benzamide> 4-{[(2-methoxy"-ediyi)-metiiyI-anmo]-meth)^}-N-[4-methoxy^7-(2-pyridin-2-yi-diiazoI- 4-yl)-benzothiazol-2-yl]-benzamide, N-(4-me^oxy,-7-morpholin^yi-benzodiiazol-2-)i)^ti^uorometh^-benzamideJ 4-fiuoro-N-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-^)-benzainide) N-(4-metiioxy--7-morphoKn-4-yl-benzothiazoI-2-yI)-benzamide, 4-cMoro-3-{[ethyl-(2-metho:^-ediyl)-amino]-met^^ benzothiazoI-2-yI)-benzamide, N-(4-methoxy-7-morphoIin-4-yl-beiizotMazol-2-yl)-3-me^ 4-cMoro-N-(4-methoxy-7-morphoIin^yi-benzothiazol-2^ benzamide, 4-cMoro-3-{[(2-methoxy-ethyl)-methyl-aniino]-me^^ yl-ben£odiiazol-2-yl)-ben2amideJ 4-cUoro-3-[C2-me&oxy^-ethyiamino)-methyl]-N-(4^methoxy;-7-inorphoIia-4-yl-- benzothiazol-2-yl)-benzamide, 3-[(2-methoxy-ethylamino)-methyl]-N-(4-metto yl)-benzamide, 3-i[(2-methoxy-ethyI)-meth)d-amiiio]-nK^yl}-N-(4-methoxy-7-moi7holin-4-yi- benzotbiazol-2-yl}-beiizaEQide, 4-[(2-etho:^-ethylamino)-methyl]-N-(4-me&^^ ben/amide, N-(4-methoxy-7-morpholin^yl-benzothiazol-2-yl)^m 4^2-dimethylamino-etbykul£mylmet^^ 2-yl)-benzaniide> 4-{[(2-ethoxy-etiayl)-etbyl-ammo]-methyl}-N-(4-methoxy-7-morpholin^yl- benzothiazol-2-yl)-benzamideJ 4-{ [(2-ethoxy-etiiyl)-methyI-amiiio] -methyl}-N-(4-nietb.oxy-7-morphdiii-4-yl- ben201iiazol-2-yl)-benzainideJ 4-(?-methoxy-ethoxyrpetby1)-N-(4-metboyy^ benzamid 4-methoxymethyI-N-(4-methoxy-7-morphoIin^yU^ N-(4-methoxy-7-tiiiomorpholin-^>d-benzothiazol-2-yl)-benzaimdeand [4-(4-metiioxy-7-moipholm-4-yl-bermilhiazol-2-^ acid methyl ester. Further preferred compounds of formula I for the above mentioned use are those, wherein R is phenyl, substituted by a optionally substituted -(CH2)n-five to seven membered aromatic or non aromatic heterocyde, for example the following compounds: 4-irmdazoI-l-yI-merhyl-N-(4-merhoxy-7-ph^ 4-(4-Hydroxy-piperidm-l-yl-methyl)-N-(4-m benzamide, 4-[l,4]diaKpan-l-yl-methyi-N-(4-methoxy-7- 4- (3 (S)-dimethylammo-pynrolidin- l-yl-methyl)-N-(4rmet]ioxy-7-phenyl-benzo1hiazol-2- yl)-benzamide, N-{4-merhoj^-7-[2-(6-merhyl-pyridm-3-yl)-t^ pyrrolidin- 1-yl-methyl-benzamide, N-(4-methoxy-7-thiophen-2-yl-benzotlriazol-2-yI)^py^ N- [4-methoxy-7-(2~pyrio^-2-yI-thiazoI^yi)-beiizothia^ I -yi- methyl-benzamide, 4-cUoro-N-(4-methoxy-7-morpholm-4-yl-ben201hiazol-2-yl)-3-pyrrohdm-l-yl-methyl- benzamide, N-(4-metho:^-7-morpholm-4-yl-benzothi^ N- (4-memoxy-7-morpholm^yl-beiizothiazol-2-yl)^(2-m benzamide and N-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-4- (4-methyI-piperazm- 1-yl-methyi)- benzamide. Especially preferred are compounds, wherein R4 is an optionally substituted five to seven membered aromatic or non aromatic heterocyde, which is for example morpholine or piperazine. Preferred compounds of formula IA are those, wherein R1 is methoxy, X is oxygen andR2/R3 are hydrogen. Exemplary preferred are compounds of formula IA, wherein R" is an unsubstituted or substituted five or six membered aromatic heterocyde, for example the following compounds: N-(4-me&oxy-7-morpholm^yl-berizotriiarol-2^ 5~methyl-tHophene-2-carboxylic add (4-memoxy-7-phenyl-benzo1hiazol-2-yi)-arnide, 5-methyl~furan-2-carboxylic add f4-metho3cy-7-pb.en)^-benzothiazol~2-jd.)-amide> N-(4-meliioxy"-7-phen^-benzo1iiiazol-2-yl)-isonicotinamide, 5-memyl-triiophene-2-carboxyiic add (4-memoxy-7-pyridm-4-yI-benzomiazol-2-yI)- amide, 5-merayl-thiophene-2-carboxv]ic add (4-methoxy-7-pyridin-3-yi-benzothiazol-2-^)- amide, 5~methyl~thiophene-2-carboxylic add [4-methoxy~7-(2-methyl-T^ridin-4-yl)- benzothiazol-2-yl] -amide, 5-metbyl~thiopliene-2-carboxyiic add [7-(3-ammo-phenyl)-4-methoxy-benzothiazol-2- yl] -amide, N-(4-memoxy-7-tHophen-2-yl-benzothiazol-2-yl)-2-me^ N- [4r-methoxyr-7-(2-pyridm-2-yl-thiazoI-4-yl)-ben2otbiazol-2-yI] -2-methyl- isonicotinamide, N- [4-methoxy-7-(2-pyrrolidin- l-vl-tHazol-4-yi)-benzotaiazol-2-yl] -2-methyi- isorucotinarnide, N-{4-methoxy-7- [2-(4-methyl-piperazin-l -yl)-tniazoI-4-yl] -benzothiazol-2-yl}-2-methyl-isonicotinamide and N- [4-metbox7-7-(5-metiiyl-"diiopheD-2-yl)-benzotbia2ol-2-yi] -2-mediyl-isonicotinamide. Further preferred compounds of formula IA are compounds, wherein R is an unsubstituted or substituted five or six membered aon aromatic heterocyde, for example the following compounds: morpholine-4-carboxylic add {4-methoxy-7-phenj4-benzothiazol-2-yl)-anude, thiomorpholine-4-carboxyJic add (4-methoxy-7-pherryi-beiizotniazol-2-yl)-amide, 1-oxo-ll 4-thiomorphoune-4-carboxylic add (4-methoxy-7-phenyl-benzothiazol-2-yl)- amide, morphoBne-4-carboxylic add {4^mettoxy-7-[2-(6~memyl-pyridm-3-yl)-tbiazol-4-yl]- benzothiazol-2-yl}-amide, morpboline-4-carboxyUc add [4-me&oxy-7-(2-pyridm-2-yl-tinazol-4-yl)-berjzotbiazol-2- yl]-amide, morpholine-4-carboxyUc add {4-memoxy-7-[2-(4-methyl-prpera2m-l-yl)-thiazol-4-yi]- benzomia2ol-2-yi}-amide1 morpholine-4-carboxyIic add [4^methoxy-7-(2-piperidm-l-yl-thiazol-4-yl)-benzotnia2ol- 2-yl]-amide, morpholine-4-carboxylic acid [4-metboxy-7-(5-methyl-thiophen-2-yI)-ben20thiazol-2- yl]-amide, 4-(4-memoxy-7-morpholm-4-yl-benzotm^2ol-2-yl-catbainoyl}-piperid^e-l-carboxyiic acid tert-butyl ester, l-acetyl-piperidine-4-carboxylic acid (4-memoxy-7-morpholin--4-yi-benzothiazoI-2-yl)- amide, 4-oxo-piperidine-l-carboxylic acid (4-methoxy-7-morpholin-4-yl-beiizotbiazol-2-yl)- amideand l-oxo-lX4-tbJomorpholme-4-carboxylic acid (4-methoxy-7-prperidm-l-yI-ben2otbia2ol- 2-yl)-amide. Preferred are further compounds, wherein R is methoxy, for example the following compounds: rac-[7-(2-bromo-l-hydroxy-emyl)-4-memoxy-benzotmazol-2-yl]-carbamic acid methyl ester, {4-methoxy-7-[2-(6-methyl-pyridm-3-yl)-tto methyl ester, [4-methoxy-7-(2-pyridm-2-yl-linazol-4-yl)-ber^ acid methyl ester, [4-melho3cy-7-(2-piperidm-l-yl-miazol^yl)-benzothia2ol-2-yl]-carbamic acid methyl ester and {4-methoxy-7- [2- (4-methyi-piperarin- l-yl)-tniazol-4-yl] -benzothiazol-2-yl}-carbamic acid methyl ester. Preferred compounds of formula IA are those, wherein R1 is phenyl, optionally substituted by -CH2OH, -CH2NHCH2CH2OCH3, -CH2NHCH2CH2OH, -CH3NHCH2.-pyridinyl -CHsNH* -CH2NHCH2CH2SCH3, -CH2N(CH3)CH2CH2SCH3,-CH2N(CH3)CH2CH20CH3, -CH2N(CH2 CH3)CH2CH2OCH3> -CH2NHCH3, -CHzSCHaCHzNfCHj)* -CHaOCHs, -CH2OCH2CH20CH3 or -CH2N(CH3)C(0)OCHj, for example the following compounds: 4-hydroxymethyl-N-(4-memoxy-7-phenyI-benzothiazoI-2-yI)-benzamide, 4- [ (2-methoxy-ethylamino)-methyl] -N-(4-methoxy-7-phenyI-ben2othiazol-2-yI)-benzamide, 4-[(2-hydrory-ethylamino)-memyl]-N-C4-methoxy-7-phenyl-benzothiazol-2-yl)^ benzamide, N-(4-memoxy-7-phrayl-benzothiazol-2-yl)-4-{[(pyri benzamide, N-(4-methoxy-7-phenyl-benzotmazol-2-yl)-4-{[(pyridm~3-ymiemyi)-ammo]-met^ benzamide, 4~aininometh^-N-(4-metiioxy"-7-phenyl-benzothiazol-2-ylJ-benzainKle, N-(4-methoxy-7-phenyl-benzothiazol-2-yi)-4- [(2~methylstilfenytediylamino)-methyl] -benzamide, 4-{[(2-methoxy-ethyl)-methyI-amino]-methyl}-N-(4-methoxy-7-morpholin-4-yi-benzothia2ol-2-yl)-benzamide, N-[7-(2-ainino-thiazol^yl)^metiioxy-benzothiazol-2-yl]-4-fluoro-beiizainide, 4-fluoro-N-{4-methoxy-7- [2-(6-methyl-pyridin-3-yl)-thia2ol-4-yi] -benzotbjazol-2-yl}-benzamide, 4M[(2-methoxy-ethyi)-metiiyl-ainino]-meth^ yI)-thiazol-4-yl]-benzoliiiazol-2-yi}-benzamide, 4-{[(2-Methoxy-ethyl)-methyl-amino]-methyI}-N-(4-metimxy-7-diiopheD--2-yl-benzothiazol-2-yl)-benzamide, 4-{ [ (2-methoxy-ethyD-methyl-amino] -methyl}-N-[4-methoxy-7-(2-pyridiii-2-yl-thia2ol-4-yl)-benzotbia2ol-2-yI] -benzamide, N-(4-methoxy-7-morpboUB-4-yl-berizoliia2oI-2-yI)^trifluorometbyl-ben2amide, N-(4-methoxy-7-morphoHn^yl-baizothia2ol-2-yi)-benzaniide, 4-cbloro-3-{[etiiyl-(2-meti.oxy-e&yI)-amino]-mediyI}-N-C4-metho^-7-moTpholiQ^yl-benzotiiiazol-2-yI)-beiizamide> N-(4-metboxy,-7-morpholin-4-yl-ben2otbiazol-2-yi)-3-methylarninometbyl-benzam 4-cb]oro-N-(4-methc^-7-morpholk>4-yl-benzo^^ benzamide, 4-cUoro-3-{[(2-melitoxy-ethyl)-meiiyI-ainino]-meliiyi}-N-(4-metho^-7-taorpholin-4-yl-benzotbiazol-2-yl)-ben2amide> 4-cHoro-3-[(2-methoxy-ethykmino)-me1byI]-N-(4-methoxy-7-morphoIin-4-yl-benzothiazol-2-yI)-benzamide, 3-[(2-metboxy-etb.ylamino)-methyl]-N-(4-m yl)-benzamide, 3-{[(2-metboxy-ethyl}-methyl-amino]-methyl}-N-C4-medioxy-7-morpholiii-4-yi-benzothiazol-2-yi) -benzamide, 4-[(2-ethoxy-ethylainino)-methyl]-N-(4-me1hoxy^ benzamide, N-(4-metbaxy-7-morpholin^)4-ben2odiiazoI-2-yl)-4-me&^ 4-(2-dimetbyIainino-e1bylsirifanyl^ 2-yl)-benzamide, 4-{[(2-ethoxy-etiiyl)-etbyl-amino]-metbyI}-N-(4-methoxy-7-morpho]iD^yi-benzothiazol-2-yl) -benzamide* 4-{[(2-elhoxy-ethyl)-methyl-ainino]-methyl}-N^^ benzothiazol-2-yl)-benzamide, 4-(2-methoxy-ethoxymethyl)-N-(4-^ benzamide, 4-memoxymethyl-N-(4-memoxy-7-mo:ipholm^yl-benz^ N-(4-methoxy-7-tbiomoipholin^-yl-benzotbia2ol-2-yl)-benzamideaiid [4-(4-methoxy-7-morphoHn^yl-benzotiiiazol-2^ acid methyl ester. Further preferred compounds of formula IA are those, wherein R" is phenyl, substituted by a optionally substituted -(CR^Vfive to seven membered aromatic or non aromatic heterocycle, for example the following compounds: 4-iimda2ol-l-yImemyl-N-(4-mefooxy-7-pta 4-(4-Hydro^-piperidm-l-yl-methyl)-N-(4-m benzamide, 4-[l,4]diazepan-l-yl-memyl-N-(4rmethoxy-7-phenyl-benzotbiazol-2-yl)-ben2am^ 4-( 3 (S)-dimethylammo-pyiToHdm-l-yl-memy yl)-benzamide, N-{4-metboxy-7- [2-( 6^memyl-pyridin-3-yi)-tbiazol-4-vl] -benzothiazol-2-yl} -4- pyrrolidin-1-yl-methyl-benzamide, N-(4-methoxy-7-thiophen-2-yl-benzothiazol-2-yl) -4-pyrrolidin- l-yl-methyl-benzamide, N-[4-memoxy-7-(2-pyridm-2-yI-tbiazoI^yI)-beiizothia^ methyl-benzamide, 4-chloro-N-(4-metiioxy-7-morpholm^yl-benzotbia2ol-2-yI)-3-pyrroKam benzamide, N- (4-memoxy-7-morpholm^yl-benzo1hia2ol-2-yl)-3-pyrrolidin-l -yl-medrjd-benzaniide, N- (4-memoxy-7-morpholm^yl-benzothiazol-2-yl)-4-(2-methyl-imidazol-1 -yl-methyl)- benzamide and N- (4~memoxy-7-morpholm^yl-benzothiazol-2-yl)-4-(4-methyl-piperazin- l-yl-methyl)- benzamide. Especially preferred are compounds of formula IA, wherein R4 is an optionally substituted five to seven membered aromatic or non aromatic heterocycle, which is for example morpholine or piperazine. The present compounds of formulas I and I-A and their pharmaceuticafly acceptable salts can be prepared by methods known in the art, for example, by processes described below, if desired, converting the compounds obtained into pharmaceuticaUy acceptable acid addition salts. All reaction steps described above are carried out in conventional manner and are described in more detail in the working examples. In accordance with process variant a) a compound of formula II, for example 2-amino-7-phenyl-4-niethoxy-ben20tbiazol in pyridine is dissolved in tetrahydrofuran and is then treated with phosgene in toluene. The reaction mixture is concentrated to half the volume under reduced pressure and the appropiate amine, for example an amine of formula R5R6NH or a cyclic amine, such as morpholine or thiomorpholine, are added. The obtained product is isolated by flash chromatography. Reaction variant b) describes the process for preparation of a compound of formula I, wherein a compound of formula II is reacting with a compound of formula IV. The reaction is carried out for about 10 minutes in conventional manner. The obtained compound is then isolated by flash chromatography. The salt formation is effected at room temperatures in accordance with methods which are known per se and which are familiar to any person skilled in the art. Not only salts with inorganic acids, but also salts with organic acids came into consideration. Hydrochlorides, hydrobromides, sulphates, nitrates, citrate, acetates, maleates, succinates, methan-sulphonates, p-toluenesulphonates and the like are examples of such salts. In Examples 1 —187 and in the following schemes 1 and 2 the preparation of compounds of formula I is described in more detail. The starting materials are known compounds or may be prepared according to methods known in the art. compounds of the present invention may be useful as sedatives, muscle relaxants, antipsychotics, antiepileptics, anticonvulsants and cardiaprotecuve agents and for the production of corresponding medicaments. The most preferred indications in accordance with the present invention are those, r which include disorders of the central nervous system, for example the treatment or prevention of certain depressive disorders, neuroprotection and Parkinson"s disease. The dosage can vary within wide limits and will, of course, have to be adjusted to the individual requirements in each particular case. In the case of oral administration the dosage for adults can vary from about 0.01 mg to about 1000 mg per day of a compound of general formula I or of the corresponding amount of a pharmaceutically acceptable salt thereof. The daily dosage may be administered as single dose or in divided doses and, in addition, the upper limit can also be exceeded when this is found to be indicated. Example 1 N- (4-Memoxv-7-phenyl-benzothiazol~2--vl) -benzamide To a solution of 2-animo^methoxy-7-phenyl-benzothiazole (100 mg, 0.4 mmol) in pyridine (2 ml) was added benzoyl chloride (55 mg, 0.4 mmol) and the mixture stirred overnight at 20 °C. To this mixture 2N HC1 to pH 1 (20 ml) was added then the mixture was extracted twice with EtOAc (20 ml), washed with saturated NaHCC>3 solution, dried with NajS04 and the solvent evaporated. The crude product was then chromatographed over Si02 (Merck 230-400 mesh) eluting with Ct^CVMeOH (98:2), the product fractions were pooled and the solvent evaporated, to afford the title compound as a white solid (97 mg, 69 % yield), MS: m/e=360 (M). Following the general method of example 1 the compounds of examples 2 to 49 were prepared Example 2 FuTan-2-carboxvuc acid (4-methoxv-7-phenyl-benzothia2ol-2-ylVamidfc Using furan-2-carboxylic acid chloride the title compound was prepared as a beige solid (41 % yield), MS: m/e= 251.3 (M+lT). Example 3 5-Methvl-\|^\|nphene-g-carbo3cy]jc acid f4-methoxy-7-phenvl-b^79bia;zoI-2-yD-aTTiide Using 5-methyi-diiophene-carbozylic acid chloride the title compound was prepared as a beige solid (36 % yield), MS: m/e= 381.3 (M+H+). Example 4 Furan-2-carboxviic acid (4,6-difluoro-berizothiazol-2-yl)-arnide Using 2-amino-4,6-difluoro-benzothiazole and fUran-2-carboxyiicacid chloride the title compound was prepared as a grey solid (81 % yield), MS: m/e= 280 (M1"). Example 5 5-Methyi-thiophene-2"Carbox>dic acid (4,6rdifluoro-benzothifl7-n)-^-yT)-amiHg Using 2-ammo^,6-^lifluoro-benzothiazoIe and 5-methyl-thiophene-carboxylicacid chloride the title compound was prepared as a yellow solid (74 % yield), MS: m/e= 310 Example 6 N- (4,6-Difluoro-benzothiazol-2-yl)-benzamide Using 2-arnino-4,6-difluoro-benzothiazole and benzoyl chloride the title compound was prepared as a beige solid (82 % yield), MS: m/e= 290 (M). Example 7 N-(4-Methoxv-7-phenvl-beiizothiazol-2-yl)-acetamide Using acetyl chloride the title compound was prepared as a light brown solid (69 % yield), MS: m/e= 299.2 (M+JT). Example 8 4-Cyano-N-f4-methoxv-7-pheayl-benzothiazol-2-yl)-benMrnidft Using 4-cyaho-benzoyl chloride the title compound was prepared as yellow solid (84 % yield), MS: m/e= 385.1 (M). Example 9 5-Methyl-thiophene-2-carboxvlic acid f4-methoxy-h"i7^hiq2ol-2-yl)-amide Using 2-ainino-4-methoxy-benzothiazole and 5-methyi-thiophene-2-carboxylic acid chloride in pyridine the title compound was obtained as a beige solid (95 % yield), MS: m/e=304.1 (M). Example 10 5-Methvl-furan-2-carboxviic acid (4-methoxy-7-phenyl-benzothia2ol-2-vlVamide Using 2-amino-4-methoxy-7-phenyl-benzothiazole and freshly prepared 5-methyl-fhran-2-carboxylic acid chloride the title compound was obtained crude, which was chromatographed over S1O2 (Merck 230-400 mesh) during with nHexane/EtOAc (4:1), to afford the pure title compound as a pale yellow solid (67 % yield), MS: m/e=364.0 (M). Example 11 Furan-2-carboxylic acid f 4-memoxv-berizo1niazoI-2-yO-amide Using 2-amino-4-methoxy-benzothiazole and furan-2-carboxylic acid chloride in pyridine the title compound was obtained as a tan solid (100 % yield), MS: m/e=274.1 (M). Example 12 N-(4-Methoxy-benro1hiazol-2-ylVben2ainide Using 2-amino-4-methoxy-benzotbiazole and benzoyl chloride in pyridine the tide compound was obtained as a white solid (72 % yield), MS: m/e=284.1 (M). Example 13 Benzo[b]thiophene-2-carboxvh^acidben7nthia7nV2-ylamide Using 2-amino-benzothiazole and benzo[b]thiophene-2-carboxyhc acid chloride in pyridine the title compound was obtained as a light yellow solid (86 % yield), MS: m/e=311.1 (M+fT). Example 14 3-Methyl-lbiophene-2-carbpxylic arid henvrithiavcA-J.-ylamicip. Using 2-amino-benzothiazole and 3-methyl-thiophene-2-carboxylic acid chloride in pyridine the title compound was obtained as a yellow solid (69 % yield), MS: m/e=275.1 (M+H). Example 15 5-Methyl-thiophene--2-caiboxvIic acid benzothiazoI-2-yIamidfi Using 2-amino-benzothiazoIe and 5-mimyl-thiophene-2-carboxyhc acid chloride in pyridine the tide compound was obtained as a yellow solid (87 % yield), MS: m/e=275.1 (M+H). Example 16 N-Benzothiazol-2-^-6-chloro-nicntinamide Using 2-araino-benzomiazole and 2-chloropyridine-5-carboxylic acid chloride in pyridine die title compound was obtained as a white solid (97 % yield), MS: m/e=290,l (M+H). Example 17 4-Hvdroxymethyl-N- (4-memoxv-7-phenvi-benzolhiazol-2-vl"}-benzamide To a solution of 4-fbrmyl-N-(4-methoxy-7-phenyl-ben2othiazol-2-yl)-benzamide (194 mg, 0.5 mmol), in THF (40 ml) was added sodium borohydride (19 mg, 0.5 mmol) and the mixture stirred for 2 h at r.t. Water was added (30 ml) followed by IN HC1 (4 ml) and the mixture agitated. The aqueous phase was then extracted twice with EtOAc (30 ml), the combined organic phases were then washed with saturated NaCl solution, dried with NasS04 filtered and evaporated. The crude residue was suspended in ether and ultrasonnicated for 10 min-, the solid precipitate was filterted off, washed with ether then dried under vacuum (0.05 mmHg, 50 °C) to afford the title compound as a light yellow solid (150 mg, 77 % yield), MS: m/e= 390.0 (M). Example 18 4-Formyl-N-(4-me&oxv-7-phenyl-beigotbia2ol-2-v^""-t\ Using 4-formyl benzoic add the title compound was obtained as a light yellow solid (73 % yield), MS: m/e=388.1 (M+H). Example 19 2-Memoyy-N-(4-methoxy-7-phenvl-ben20thiazol-2--vlVbf!n7arni^f- To a solution of 2-amino-4-methoxy-7-phenyl-benzothiazole (200 mg, 0.67 mmol) in THF (10 m) was added DMAP (10 mg, 0.08 mmol), triethylamme (163 pi, 1.17 mmol) and 2-mboxybeim37lchkmdetl36MKlmiTw>i)mT reflux for 2 h, after cooling, it was partitioned between 1:1 AcOEt/THF (70 ml) and 5% NaHC03 solution( 40 ml). The organic phase was washed with saturated NaCl solution (50 ml), dried with Na2S04, filtered and the solvent removed under reduced presure. The residue was suspended in ether (10 ml), filtered, washed with ether then dried under vacuum (0.05 mmHg, 60 °C), to afford the title compound was a white solid (260 mg, 85 % yield), MS: m/e= 390.0 (M). Example 20 N-f4-Meriiogy-7-phenvl-beiizothiazoI-2-vl)-2-metliyl--benzarnide Using 2-methyl-benzoyI chloride the title compound was obtained crude, which was chromatographed over Si03 (Merck 230-400 mesh) eluting with O^CVEtOAc (1:1), to afford the pure title compound as a white solid, (88 % yield), MS: m/e=374.3 (ht). Example 21 N-f4-Metlioxy-7-phenyl-benzothiazol-2-ylV3-meth.Yl-benzamide Using 3-methyl-ben2oyl chloride the title compound was obtained crude, which was chromatographed over Si02 (Merck 230-400 mesh) eluting with Cf^CVEtOAc (1:1), to afford the pure title compound as a light yellow solid, (80 % yield), MS: m/e=374.0 (M1"). Example 22 N-(4~Metlioxv-7-pheny]-hffn7omiazol-2-yl^-4-meth.yl-bgn7aTTiiHf; Using 4-methyi-benzoyl chloride the title compound was obtained crude, which was chromatographed over Si02 (Merck 230-400 mesh) eluting with CH2Cl2/EtOAc (1:1), to afford the pure title compound as a white solid, (79 % yield), MS: m/e=374.1 (M). Example 23 4-Huoro-N-f4-memoxv-7-pheriyI-benzotriiazol-2-yl)-ben2arnide Using 4-fluoro-benzoyl chloride the title compound was obtained crude, which was chromatographed over SiC^ (Merck 230-400 mesh) eluting with CHzCb/EtQAc (1:1), to afford die pure title compound as a white solid (68 % yield), MS: m/e=378.0 (M). Example 24 3-Memoxv-N-("4-methoxy-7-phenyl-^"7-"t^ia7ol-2-yl)-hen»aTniHf" Using 3-methoxy-benzoyl chloride the title compound was obtained crude, which was chromatographed over Si02 (Merck 230-400 mesh) eluting with CH2Cl2/EtOAc (1:1), to afford the pure title compound as a light yellow foam (75 % yield), MS: m/$=390.0 (M). Example 25 4-Methoyy-N-(4-memoxy"7-phenyl-benzotJiia2ol-7-y1)-hnMTTiiHi» Using 4-methoxy-benzoyl chloride the title compound was obtained crude, which was chromatographed over Si02 (Merck 230-400 mesh) eluting with CH2Cl2/EtOAc (1:1), to afford the pure title compound as a white foam (79 % yield), MS: m/e=390.i (M). Example 26 N-(4-Methoxy-7-phenyl-benzothiazol-2-vl)-2-phenyl-acetamide Using phenylacetyl-chloride chloride the tide compound was obtained crude, which was chromatographed over Si02 (Merck 230-400 mesh) eluting with CH2Cl2/EtOAc (1:1), to afford the pure tide compound as a white solid (29 % yield), MS: m/e=374.1 (M). Example 27 3-Methvl-thiophene-2-carboxyiic acid (4-metboxy-7-phenyl-benzothiazoi-7.-yT)-aTniHf» Using 3-in^yJ-tbj0ribrae-2-carbaxylicarid chloride tie title compound w&s obtained crude, which was chromatographed over Si02 (Merck 230-400 mesh) eluting with CEbCh/EtOAc (1:1), to afford the pure title compound as a white solid (64 % yield), MS: m/e=380.0 (M+). Example 28 2,5-Dimethyi-fttran-3-carboxjdic acid (4-memoxy-7-phenyl-benzothia2oI-a-Yl)-amirie Using 2,5-dimemyl-furan-3-carboxylicaad chloride the tide compound was obtained crude, which was chromatographed over Si02 (Merck 230-400 mesh) elutiiig with CH2Cl2/EtOAc (1:1), to afford the pure tide compound as a white solid (73 % yield), MS: m/e=378.1 (M+). Example 29 3-Cyano-N-f4-methoxy-7-phenyl-benzothiazol-2-yl^-bCTi7aiTiiflp using ^-cyano-benzoyl cnlonde toe title compound was obtained crude, which was chromatographed over Si02 (Merck 230-400 mesh) eluting with CH2Cl2/EtOAc (1:1), to afford the pure title compound as a white solid (80 % yield), MS: m/e=385.0 (M+). Example 30 " N-f4-Methoxy-7-phenoyy-benzomiazol-2-1id)-benzamide Using 4-Memoxy-7-phenoxy-beiizothiazol-2-ylamine and benzoyl chloride the title compound was obtained crude, which was chromatographed over Si2 (Merck 230-400 mesh) eluting with CrkCU/EtOAc (1:1), to afford the pure title compound as a white solid (72 % yield), MS: m/e=376.1 (M)- Example 31 4-Dimemykmmo-N-(4-methor^-7-pheDvI-ben2adiiazol-2-vl)-benzarnide Using 4-dimethylamino-benzovl chloride in pyridine the title compound was obtained crude, which was chromatographed over Si02 (Merck 230-400 mesh) eluting with CH2CV(2N NH3inMeOH) (19:1), to afford the pure title compound as a beige solid (70 % yield), MS: m/e=403.0 (M"). Example 32 4-Huoro-N-(4-methoxy-7-phenyl-bpTi?r>t^iqzol-2-ylVN-metfav^-Vipn7-flTrii^e Using (4-nimethoxy-7-phenyl-benzo11uazol-2-yl)-methyl-amine and 4-fluoro-benzoyl chloride in pyridine the title compound was obtained crude, which was chromatographed over Si02 (Merck 230-400 mesh) eluting with CH2Cl2/EtOAc (1:1), to afford the pure title compound as a beige solid (88 % yield), MS: m/e=393.2 (M+H). Example 33 2-(4-HuorcHbeng^aTninn^-4-memoxv-benzolfaiazole-7-carboxyhc acid methyl ester Using 2-ammo-4-medioxy-benzothiazole-7-carboxyhc acid methyl ester and 4-fluoro-benzoyl chloride the title compound was obtained as a white solid (91 % yield), MS: m/e=361.1 (M+H+). Example 34 N-f7-teit-Bu1vl-4-memoxy-beriZ01hiazol-2-vl)-4-fluoro-benzarnide I " Using 7-tert-butyl-4-memoxy-benzothiazol-2-ylarnine and 4-fluoro-benzoyl chloride die tide compound was obtained as a white solid (75 % yield), MS: m/e=258.1 (M+H). Example 35 N-f7-Acel7^airiiTio-4-mel3ioxv-benzotmazol-2-yl)^"fluoro-benzamide Using 7-acetylammo-4-memoxy-benzothiazoI-2-ylamrne and 4-fluoro-benzoyl chloride the title compound was obtained as a tan solid (25 % yield), MS: m/e=359.1 (M+H). Example 36 N- (4-Methoxy-7-phenyl-beHzothiazol-2-yt1-isonir-ntinamiH e Using pyridine-4-carboxyiic acid chloride hydrochloride salt in pyridine the tide compound was obtained crude. After cooling a solid precipitated from the reaction mixture which was further triturated with ether (10 ml) then collected on a glass sinter and further washed with ether (10 ml). The filter cake was then washed sequentially with 10% Na2C03 (20 ml), water (20 ml) followed by ether (20 ml) and the resulting product dried under vacuum (0.05 inmHg, 60 °C) to afford the pure title compound as a yellow solid (188 mg, 67 % yield), MS: m/e=361.0 (M+). Example 37 4-Fluoro-N- (4-metfaoxy-7-phenoxy-beri7.othia7.nl -2-yl)-benzamide Using 4-metiioxy-7-phenoxy-benzothiazol-2-ylamine and 4-fluoro-benzoyl chloride the title compound was obtained crude, which was chromatographed over SiC>2 (Merck 230-400 mesh) eluting with CH^Cb/EtOAc (1:1), to afford the pure title compound as a white solid (75 % yield), MS: m/e=394.1 (M+). Example 38 5-Methyl-thiophene-2-carboxyIic acid (4-methoxv,-7-phenoxv-benzotbia7.ol-2-vIVamide Using 4-metJioxy-7-phenoxy-benzothiazol-2-viarnine and 5-methyl-thiophene-2-carboxyhc acid chloride the title compound was obtained crude, which was chromatographed over Si02 (Merck 230-400 mesh) eluting with CHjCb/EtOAc (1:1), to afford the pure title compound as a pale yellow solid (76 % yield), MS: m/e=396.0 (M"). Example 39 4-Huoro-N-(4-methoxv-7-morpholm-4-ylmefryl-ben?^^ Using 4-meth.oxy-7-morpholin-4-ylmethyI-ben20t}iiazol-2-yiamiiw and 4-fluoro-benzoyi chloride in pyridine the title compound was obtained as a yellow solid (44 % yield), MS: m/e=402.4 (M+H). Example 40 5-Metbyl-tbjophene-2-carboxvlic add (4-methoxv-7-morphn1in-4-vlinethvi-benzothiazol-2-yl)-amide Using 4-methoxy-7-morphoiin-4^ylmethyl-beDaotMazoI-2-ylanune and 5-methyi-tbiophene-2-carboxyUc add chloride in pyridine the title compound was obtained as a yellow solid (53 % yield), MS: m/e=404.4 (M+H1"). Example 41 4-Huoro-N-[4-memoxv-7-flH-telTa2ol-5-yl)-benzo1luazol-2-yl1-benzamide Using 4-methoxy-7-( lH-tetrazol-5-yl)-beiizotniazol-2-ylamine and 4-fluoro-benzoyl chloride in pyridine the title compound was obtained as a tan solid (70 % yield), MS: m/e=371.2 (M+H). Example 42 N-BenzotHa"ml-3-vl-benzamide Using 2-amino-benzothiazole and benzoyl chloride in pyridine the title compound was obtained as a white solid (87 % yield), MS: m/e=255.1 (M+H). Example 43 Furan-2-carboxyiic add benzothiazol-2-ylamide Using 2-amiho-benzothiazole and furan-2-caiboxylic add chloride in pyridine the title compound was obtained as a white solid (83 % yield), MS: m/e=244 (M). Example 44 2-CMoro-N-(4-meth^-2-benzotfaiazoIyi)-nicotinamide Using 4-memyl-benzothia2ol-2-ylamine and 2-chloronicotinic add chloride the title compound was obtained as a yellow solid (50% yield), MS: m/e= 304 (M+H1-). Jsxampie4D 2"chloro-N-f4-memoxy-2-beiizothia2oM-nicotinamide Using 4-memoxy-benzothiazol-2-yiamine and 2-chloronicotinic acid chloride the title compound was obtained as a off-white solid (50% yield). MS: m/e= 320 (M+H1-). Example 46 3-f4-Memoxv-bem^tbiazol-2-ylcarbarooyl)-acrylicacid ethyl ester Using 4-metiioxy-ben2otmazol-2-ylamine and 3-chlorocarbonvl-acryiic acid methyl ester the title compound was obtained as a off-white solid (50% yield). MS: m/e= 307 (M). Example 47 N-(4-Methoxy-7-phenyl-beny.othiazol-2-yl)-nyalaTnir acid ethyl ester The tide compound is described in the following patent literature and was prepared according to the procedure described therin. N-(Benzothiazol-2-yl)oxamic add derivatives. W. Winter, M. Thiel, A. Roesch and O. H. Wflnelms, German Patent, DE 2656468,1978. Up, 138-J42°C,MS: m/e=357 (M+H). Example 48 4-nimfthylaTYimo-N-(4-methoxy-7-phenyI-benzothiazoI-2-yl)-bertzarmde Using pyridine-2-carboxyUc acid, chloride hydrochloride salt in pyridine the title compound was obtained crude. This compound was purified further with preparative reversed phase HPLC using a Nucleosil N-proteced column (20 mmx50 mm) and eluting with a gradient of MeCN/ water (0.1 % TFA), The product fractions were pooled, evaporated and the residue partitioned between EtOAc (30 ml) and 10 % Na2C03 (30 ml) and the aqueous phase extrteacted once with EtOAc (30 ml) The combind organic phases were then washed with satuarated NaC3,.dried, fitered and evaporated to afford the pure title compound as a beige solid (110 mg, 39 % yield), MS: m/e=361.1 (M1"). Example 49 4-Fluoro-N-( 7-hydroxymetiiYl-4-methoxv-benothiazol-2-yl )V>pn7amide To a solution of 2-(4-fluoro-beri2oylammo)^methoxy-beiizotniazole-7-carboxyiic acid methyl ester (1.1 g, 3.05 mmol) in THF (250 ml) uner argon at 5 «C was added a solution of !NIiAlr^mTrg(2mr,2mTM)oTcr5-inm.,t^ then over 1 h allowed to warm to 20 °C. A further 3.5 ml of IN LiAIIVTHF was then added dropwise and the mixture stirred a further 2h at 20 °C. A solution of 5 ml THF/Water (4:1) was then added cautiosly followed by 4N NaOH (2 ml), then water (2 ml) and the mixture stirred vigorously for 15 min. Excess Na2S04 (50 g) was then added with vigorous stirring, then the solution was filtered and the solvent evaporated to afford fher title compound as a white solid (0.9 g, 89 % yield), MS: m/e=333.2 (M+H). Example 50 4-Dipropylsn1fiiTTioyl-N-f4-methoxy-7-phenvl-benzo1hia2ol-2-yl)-H^yaTnide To a suspension of 4-dipropyisulramoyi-benzoic acid (185 mg, 0.65 mmol) in toluene (10 ml) was added thionylchloride (600 mg, 5 mmol) and the mixture heated to 80 °C for 17 h. After cooling the solvent was evaporated and the resudue was taken up in THF (20 ml), 2-arrn^c^-memoxy-7-phenyl-ben2othiazole (128 mg, 0.5 mmol), triethyiarnme (105 ul, 0.75 mmol), and DMAP (6 mg, 0.05 mmol) were then added and the mixture was stirred for 1 hour at r.L followed by 1 hour at 60 °C. After cooling to r.t the reaction raixture was quenched by addition of 10 % aq. Na2C03 solution (30 ml) and EtOAc (30 ml) and vigorous stirring. After separation of the phases the aqueous phase was extracted with EtOAc (30 ml) and the combined orgainc phases were washed with 10 % aq. Na2C03, dried with NaaSCU, filtered and evaporated. The residue was then chromatographed over Si02 (Merck 230-400 mesh) eluting with a gradient of cydohexane/EtOAc from (1:4) to 100 % EtOAc. After pooling and evaporation of the product fractions the title compound was obtained as a white solid (240 mg, 92 % yield), MS: m/e=524^ (M+rT). Following the general method of example 50 the compounds of examples 51 to 53 were prepared Example 51 4-Diemylsuifamovl-N-f4-memoxv-7-phenYl-bertzotm^ol-2-yJ)-bfm7amiHe Using 4-diethylsulfamoyl-ben2oic acid the title compound was obtained as a light yellow solid (81 % yield), MS: m/e=496.2 (M+rT). Example 52 N-(4-Memoxv-7-phenvl-benzothiazol-2-yl)^(morphn1me^sulfonvlVbenzamide Using 4-(morpriomie^sulfonyl)-benzoic add the title compound was obtained as white amorphous solid (32 % yield), MS: m/e=510.3 (M+rT). Example 53 4-£th^dsuIfamovI-N-f4-methoxy-7-phenyi-benzothiazoI-2-yI)-benzamide Using 4-ethylsulfamoyl-benzoic add the title compound was obtained as pale yellow amorphous solid (20 % yield), MS: m/e=4662 (M-H)". Example 54 5-Methyl-fliiophene-2-carboxYUc add f 7-iodo-4-memoxy-benzothiazol-?.-v1)-amid" lodination of 5-methyl-thiopliene-2-carboxyiic add (4-methoxy-benzothia2ol-2-yl)-amide (5.17 g, 17 mmol) with iodine monodiloride (2.26 ml, 44 mmol), sodium acetate (3.63 g, 44 mmol) and acetic add (200 ml) in the same manner as described for (4-methoxy-benzothiazol-2-yl)-carbamic add methyl ester affords the product as off-white solid in 93% yield. MS: m/e= 430 (M). (7-Aryl-4-methoxy-ben2othia2ol-2-yI)-carbamic add ester, aryl-carboxylic add (7-aryl-4-methoxy-benzothiazol-2-yl)-amides and substituted (4-memoxy-7-aryl-benzQthiazol-2- yl)-ureas: General procedure A: (7-Iodc«4-methoxy-benzothiazol-2-yl)-carbamic add ester or the respective aryl-carboxylic add (7-iodo-4-memoxy-benzothiazol-2-yI)-amide or the respective (4-methoxy-7-aryl-benzothiazol-2-yI)-urea (1 part), the appropriate boronic add (or its ester) (1.5 equivalents), palladium(II) acetate (0.05 equivalents), potassium phosphate (2.5 equivalents) and 2-biphenyl-dicydohexyl phospbine (0.1 equivalents) are combined in toluene (20 parts) and heated in an atmosphere of argon to 65 °C for 12 hours. The reaction mixture is evaporated to dryness and the product isolated by flash chromatography (silica, eluent ethyl acetate/cydohexane 2:1). General procedure B: (7-Iodo-4-memoxy-beri2othiazol-2-yl)-carbamic add ester or the respective aryl-carboxylic add (7-iodo-4-methoxy-benzorhiazoI-2-yl)-amide amide or the respective (4-memoxy-7-aryI-berizothiazol-2-yl)-urea (1 part), the appropriate aryltrimethylstannane (1.5 equivalents), triphenylarsine (0.5 equivalents), tris-(dibenzylideneacetone)-dipalladium(O) (0.8 equivalents) and copper(I)iodide (0.8 equivalents) are combined in dirnethylformamide (25 parts) and heated to 80 °C for 12 hours. The reaction mixture is evaporated to dryness and the product isolated by flash chromatography (silica, eluent ethyi acetate). Following the general method the compounds of examples 55 to 62 were prepared Example 55 5-Methvl-thiophene-2-carboxylic add r7-f2-diloro-phenvD-4-methox7-benzothiazol--2-vl] -amide 5-MethyI-thiopbene-2-carboxyUc add [7-(2-chloro-phenyl)-4-methoxy-benzothiazol-2-yi]-amide is synthesized from 5-methyi-thiophene-2-carboxyiic add (7-iodo-4-methoxy-benzothazol-2-yl)-amidie (100 mg, 0.23 mmol) and 2-chlorophenylboronic add (54 mg> 0.35 mmol) using the general procedure A as a light yellow solid in 80% yield. MS: m/e= 415 (M+H+). Example 56 5-Methyl-thiophene-2-carbo3ndic add [4-methoxy-7-(3-nitro-phenyi)-bengftfbifl7.Al-?-yt"j -amide 5-Methyl-thiophene-2-carboxyiic add [7-(3-nitro-phenyl)-4-methoxy-benzotbia2ol-2-yl]-amide is synthesized from 5-memyl-thiophene-2-carboxyiic add (7-iodo-4-methoxy-benzothiazol-2-yl)-amide (155 mg, 0.36 mmol) and 3-nitrophenyIboronic add (135 mg, 0.81 mmol) using the general procedure A as alight yellow crystalls in 42% yield. MS: m/e= 425 (M4"). Example 57 5-Methyi-tfaiophene-2-carboxvuc add f743-dimettvyfoTTiiffo-phenvD-4-methoxy-benzo-thiazol-2-Yl] -amide 5-Methyl-tbiophene-2-carboxyUc add [7- (3-dimethylarnino-phenyl)-4-methoxy-benzothiazol-2-yl] -amide is synthesized from 5-methyl-thiophene-2-carboxyiic add (7-iodo-4-metiioxy-berizotbiazol-2-yl)-amide (100 mg, 0.23 mmol) and 3-dimediylaminophenylboronic add (58 mg, 0.35 mmol) using the general procedure A as a light yellow solid in 71% yield. MS: m/e= 424 (M+rT). Example 58 5-Methyl-i"biopbene-2-carboxylic add (4-methoxy-7-pvri6m.-4-yl-ben7x)thiazol-2-vl)--amide 5-Methyl-thiophene-2-carboxylic add (4-methoxy-7-pyridin-4-yi-benzothiazol-2-yl)-amide is synthesized from 5-methyl-tibiophene-2-carboxyHc add (7-bromo-4-methoxy- benzomiazol-2-yl)-amide (192 mg, 0.50 mmol) and 4-pyridyIboronic acid (92 mg, 0.75 mmol) using the general procedure A as a white solid in 6% yield. MS: m/e^ 381 (M). Example 59 5-Memyl-thiophene-2-carboxyUc acid f4-memoxv-7-pvridin-3-yl-benzoniiazol-2-Yl"l-amide 5-Methyl-thiophene-2-carboxylic acid (4-memoxy-7-pyridin-3-yi-berizothiazol-2-yl)-amide is synthesized from 5-methyi-tbiophene-2-carboxyiic add (7-bromo-4-methoxy-benzothiazol-2-yl)-amide (192 mg, 0.50 mmol) and 4-pyridyiboronic acid (123 mg, 1.0 mmol) using the general procedure A as a white solid in 8% yield. MS: m/e= 381 (M). Example 60 5-Methyi-thiophene-2-carboxylic acid f4-metfaoyv-7-pyridin-2--yl-ben7ntHia7.nl-2-yl"l-amide 5-Methyl-thiophene-2-carboxylic acid (4-methoxy-7-pyridm-2-yl-benzothiazol-2-yl)-amide is synthesized from 5-methyl-thiophene-2-carboxylic acid (7-iodo-4-methoxy-benzotiuazol-2-yl)-ainide (100 mg, 0.23 mmol) and 2-tri-n-butylstannane (130 mg, 035 mmol) using the general procedure B as a white solid in 23 % yield. MS: m/e= 382 (M+H). Example 61 5-Methyl-thiophene-2-carboxybc acid [4-methoxy-7-f2-methyl-pyriflin-4-v^V hpn?nthia7.o1 -2-y!] -amide 5-Methyl-thiophene-2-carboxyUc acid [4-methoxy-7-(2-methyl-pyridin-4-yI)-benzothiazol-2-yl]-amide is synthesized from 5-memyl-thiophene-2-carboxyuc acid (4-meuioxy-7-iodo-benzothiazol-2-yl)-amide (260 mg, 0.60 mmol) and 2-methyl-4-trimethylstannanyl-pyridine (384 mg, 0.90 mmol) using the general procedure B as a light yellow solid in 50% yield. MS: m/e= 396 (M+H). Example 62 5-Memyl-thmphene-2-carboxvlic acid [7-f3-amino-phenvl)-4-metho]ry-ben?.r>thTazol-2-yil-amide 5-Methyl-thiophene-2-carboxyiic acid [7-(3-ammo-phenyl)-4-memQry-benzothiazol-2-yl]-amide is synthesized from 5-methyl-thiophene-2-carboxylic add (4-methoxy-7-iodo- benzotbiazol-2-yl)-ainide (300 mg, 0.70 mmol) and 3-trimethylstannanyl-phen,jdamine (291 mg, 1.14 mmol) using the general procedure B as a light brown solid in 56% yield. MS: m/e= 396 (M+it). Example 63 5-Methvi-thiophene-2-carboxyhc add f4-hvdroxy-7-phenvi-benzothia7-nl-?.-y1)-anniHp A solution of 5-methyl-thiophene-2-carboxylic add (4-methoxy-7-phenyl-benzodiiazol-2-yi)-amide (630 mg, 1.7 mmol) is slowly trated with boron tribromide (16 ml, 1.0 M in dicbloromethane) at 0 °C. The reaction is slowly wanned to ambient temperature and stirred for further 72 h. The mixture is diluted with ethyl acetate and extracted twice with water and once with brine. After drying over sodium sulfate, the solvent is removed in vacuo. Hash chromatography (silica, eluent ethyl acetate/hexane 1:1) and final recrystallization from tetrahydroforane/hexarie yields 118 mg (19 %) of the product as white solid. MS: m/e= 367 (M+H). Example 64 4-l4-Methoxy-2-ff5-memyl-truophene-2-carbonvl)-ammo\|-benzomiazoI-7-yll-pipf»r37ine-l-carbQxylic add benzyl ester The title compound was synthesized starting from N-benzyloxycarbonylpiperazine and 4-bromo-2-mtroanisole as described for 5-methyl-thiophene-2-carboxylic add (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide and obtained as a white solid in 12 % overall yield, MS: m/e= 523 (M+H). Example 655-Methvi-thiophene-2-carboxvlic add f7-f3-dimemviamino-pyrrolidiTi-1-yi^-4-metho3cy-benzothiazol-2-yl1 -amide The title compound is synthesized starting from 3-(dimetn)iamino)pyrrolidine and 4-bromo-2-nitroanisole as described for 5-methyl-thiophene-2-carboxylic add (4-methoxy-7-moipholm-4-yl-b«nzothiazol-2-yl)-amide and was obtained as yellow solid in 10% overall yield, MS: m/e= 417 (M+H). Example 66 5-Methvl-tbiophene-2-carboxyhc add f5-memoxv-7-Dhenvi-benzothia2ol~2-vl)-arnide 2-Amino-5-methoxy-7-phenyIben20thiazol (45 mg, 0.18 mmol) is dissolved in dichloromethane (2 ml) and subsequently treated with triethylamine (0.073 ml, 0.53 mmol) and 5-methyl-thiophene-2-carbonyl chloride (56 mg, 0.35 mmol). After 6 fa, further 0.073 ml, 0.53 mmol) and 5-methyi-thiophene-2-carbonyl chloride (56 mg, 035 mmol) are added and the mixture is stirred for additional 18 h at ambient After addition of 0.1M aqueous sodium hydroxide, the mixture is stirred for additional 16 h. The organic layer is separated, dried and evaporated to dryness. Flash chromatography (silica, eluent ethyl acetate/cyclohexane 1:1, containing 0.5 % of 25 % aqueous ammonia) affords (10 mg, 5%) of the product as white solid. MS: m/e= 380 (M). Example 67 5-Methyl-thiophene-2-carboxyuc acid (4,5-dimemoxy-berm3truazol-2-ylVamide 2-Ammo^,5-dimethoxybanzothiazole (1.1 g, 5.3 mmol) and N,N.dimemylaminopyridine (47 mg, 0.37 mmol) are dissolved in pyridine (17 ml) and slowly treated with 5-methyl-thiophene-2-carbonyl chloride (1.5 g, 9.0 mmol). After 48 h at ambient temperature, the solution is evaporated to drynes. Hash chromatography (silica, eluent diethyl ether/cyclohexane 2:1) affords the product (618 mg, 35 %) as light yeHow solid. Example 68 5-MemvI-tIiiophene-2-carboxyIic acid (4-cUoro-bm7nthia7ol-2-yD-amide 2-Amino-4-chlorobenzothiazol (92 mg, 0.50 mmol) is dissolved in dichloromethane (10 ml) and treated with pyridine (0.060 ml, 0.75 mmol) and 5-merayl-thiophene-2-carbonyl chloride (97 mg, 0.60 mmol). The reaction mixture is stirred at ambient temperature for 18 h and then evaporated to dryness. The residue is redissolved in ethyl acetate and water, the phases are separated and the organic layer extracted with brine. After dryin with sodium silfate, the solvent is removed in vacuo Flash chromatography on silica (eluent ethyl acetate/cyclohexane 1:4 affords the product as white solid.(88 mg, 57 %). MS: m/e= 308 Example 69 S-Meravl-thiophene-2-carboxya"c acid f7-broroo-4-me&oxy-benzothi37"1-2-T^-amidg 2-Amino--7-bromo-4-methoxybenzothia2ol (2.33 g, 9 mmol) is dissolved in dichloromethane (100 ml) and at 0 °C treated with pyridine (2.2 ml, 27 mmol) and 5-methyl-thiophene-2-carbonyl chloride (2.2 g, 13.5 mmol). The reaction mixture is allowed to warm to room temperature and after stirring for additional 18 h quenched with water (100 ml). After separation of the phases, the aqueous phases are extracted twice with ethyl acetate. The f"ir4"i>^^rgHiKlay«roaf"titf" yflshpri M"h Win?! ^vi^ ;HI^ ^g^pontM n dryness. Flash chromatography on silica (eluent ethyl acetate/cyclohexane 1:1 to 4:1) and final recrystallization from ethyl acetate affords the product as off-white solid. (34 mg, 69%). MS: m/e= 384 (M). Example 70 S-Methvl-t-hinphene-2-carboxyIic acid f4-fluoro-ben2othiazol-2-^")-amide 2-Amino-4-flourobenzothia2ol (84 mg, 0.50 mmol) is dissolved in pyridine (3 ml) and treated with 4-dimethylaminopyridine (1 mg) and 5-methyl-thiophene-2-carbonyl chloride (161 mg, 1.0 mmol). After stirring for 1 h at ambient temperature, the reaction mixture was evaporated to dryness. Hash chromatography on silica (eluent diethyl ether/cyclohexane 1:1 containing 0.5 % of 25 % aqueous ammonia) and final recrystallization from ethyl acetate affords the product as off-white soIid,(34 mg, 69 %). MS: m/e= 292 (M). Example 71 5-Methvl-thiophene-2-carboxviic acid (4-trifluoromethoxy-benzothiazol-2-y1)-aniifip 2-anmio-4-triflouromethoxybenzothiazol (70 mg, 0.30 mmol) is dissolved in pyridine (3 ml) and treated with 4-dhnemylarrdnopyridine (1 mg) and 5-methyl-thiophene-2-carbonyi chloride (96 mg, 0.60 mmol). After stirring for 4 h at ambient temperature, the reaction mixture was evaporated to dryness. Flash chromatography on silica (eluent ethyl acetate/cyclohexane 1:2) affords the product as white solid. (42 mg, 39 % yield). MS: m/e= 358 (M+). Following the general method of example I, the compounds of examples 72 to 75 were prepared Example 72 5-Methyl-tbinp>iene-2-carboxvIic acid (4-methoxv-7-morpholin-4-vl-berizothiazol-2-vl)-amide Using 5-methyl-thiophene-2-carbonyl chloride and 2-amino-4-raethoxy-7-morpholin-4-yl-benzofhiazol die tide compound was obtained as a yellow solid in 97 % yield. MS: m/e= 390 (M+ET). Example 73 6-Hvdroxy-pyriHinp-7.-rarboxv1ic acid f4-methoxy-ben7-nthia7^1-2-v1)-amidp Using 2-Amino-4-methoiybenzothia2ole (450 mg, 2.5 mmol) and 6-hydroSypicolinic acid chloride (1.5 g, 10 mmol) the tide compound was obtained as a beige powder in 5 % yield. MS: m/e= 301 (Ivf). Example 74 5-Meth^-thinphpne-2-carbr)xylic acid (7-benzyioxy-4-memoxy-ben2otbia7nl-^-Y^)~aTT1^"" Using 5-memyl-thiophene-2-carboxyhc acid chloride the title compound was obtained as an off-white solid (51 % yield). M.p.: 228-230 °C. FoUowingihe general method of example 1, the compound of example 75 was prepared Example 75 6-Chloro-N-f4-memoxv-7-phenTd-ben2X>miazol-2-yl)-nicotinamide Using 6-chloro-nicotinyl chloride the title compound was obtained as a light yellow amorphous solid (79 % yield), MS: m/e=395.1 (M). Example 76 N-(4-Methoyy-7-phenyl-beiiznthia7oI-2-yl)-6-pyrrolidin- 1-yl-n ientinamiHg To a solution of 6-chloro-N-(4-memoxy-7-phenyl-beiizothiazol-2-yl)-nicorinamide (297 mg, 0.75 mmol) in dioxane (10 ml) was added pyrrolidine (265 mg, 3.7 mmol, 5 eq.) and the mixture stirred at 100 °C for 2 h. After cooling the solvent was evaporated and the residue suspended in methanol (20 ml) at r.L, the solid was then filtered, washed with methanol and finally dried under vacuum (0.05 mmHg, 60 °C) to obtain die title compound as a white solid (230 mg, 71 % yield), MS: m/e=431.4 (M+H1"). Following the general method of example 76, the compounds of examples 77 to 80 were prepared Example 77 3,4,5,6-TetrahYdro-2H-ro"1bipvridinvl-5"-carboxvlic acid (4-methoxv-7-phe^yIz benzotiiia7.nl -2-vTl-amiHe Using piperidine the title compound was obtained as a light brown solid (59 % yield), MS: m/e=445.3 (M+H). Example 78 N-(4-Mdfaoxv-7-phenyl-benzothia2ol-2-yl)^morphoIm-4-Yl-nicotinainide Using morpholine the title compound was obtained as a white solid (82 % yield), MS: m/e=447.2 (M+H). Example 79 N-(4-Methoxv-7-phenyl-benzothiazol-2-vl")-6- f 4-methyl-pip Using N-methyrpiperazine the title compound was obtained as a light brown solid (52 % yield), MS: m/e=460.4 (M+H). Example 80 N-f4-MethcCT-7-phenyl-benzothiazol-2-Yl)-6-thiomo^ hydrochloride salt (1:1) Using thiomorpholine the free base of the title compound was obtained, which was then conveted to the hydrochloride salt by addition of 5N HCl/EtOH, affording the title compound as a white solid (78 % yield), MS: m/e=463.1 (M+H). Example 81 N-(4-Metiioxy-7-phenyl-ben20thia2ol-2-yl)^-fl-oxo-ll4-tMomorpholm-4-yi"l-nirntinaTTude hydrochloride salt (1:1) To a solution of N-(4-melhoxy-7-phenyl-benzothia2ol-2-7l)-6-tMomorpholin-4-yl-nicotinamide hydrochloride salt (250 mg, 0.54 mmol) in chloroform (12 ml) was added 3-phenyl-2-(phenylsulfonyl)oxazmdine (211 mg, 0.81 mmol) and the mixture stirred at r.t for 2 hr. After evaporation of the solvent, the residue was suspended in CH2Q21 ultrasonnicated, then the precipitate was filtered oft washed with CH2G2, followed by ether and finally dried under vacuum (0.05 mmHg, 60 °C) to obtain the title compound as a light yellow solid (240 mg., 86 % yield), MS: mie=4Z92 (M+H). Example 82 4-Bromome1hvi-N-f4-memoxv-7-phenvl-beri2othia2o1-^-Yl)-hpn7aTTiide To a solution of 4-bromomethyl-benzoic acid (5.45 g, 253 mmol) in toluene (60 ml) was aH^H hi""yi "■hi"""* (18.25 ml, 25.3 mmol) and the mixture stirred at 80 °C for 16 h. The toluene and excess thionyl chloirde were then evaporated in vacuo and replaced with THF (100 ml). To this solution was added 2-ammo-4-methoxy-7-phenyl-beiizotbiazole (5 g, 19.5 mmol), triethyiamhie (4.1 ml, 29.2 mmol) and DMAP (238 mg, 2 mmol) as catalyst, then the mixture stirred at 65 °C for 4 h. After cooling the reaction mixture was partitioned between 10% aq. Na2C03 (200 ml) and EtOAc (100 ml), the aqueous phase was extracte further with EtOAc/THF (1:1) (150 ml), then the combined organic phases were washed with satd. aq. NaCl (100 ml), dried (Na2SO), filtered and evaporated in vacuo. The residue was then chromatographed over Si02 (Merck 230-400 mesh) eluting with a gradient of O^CyEtOAc (100 % CH2Q2 to 1:1), the product fractions were pooled and evaporated in vacuo to affords the title compound as a pale yellow solid (4.9 g, 55 % yield), MS: m/e=452.0 (M). Example 83 N-(4-Methoxy-7-phenvl-beiizothiazol-2-yl)-47pyrroUdm-l-ylmemyl-berizarnide hydrochloride salt (1:1) To a solution of 4-fonnyl-N-(4-methoxy-7-phenyl-ben2othiazol-2-yl)-ben2ainide (300 mg, 0.77 mmol) in THF (60 ml) was added pyrrolidine (82 mg, 1.16 mmol), acetic acid (70 mg, 1.16 mmol) and NaBFJ(OAc)3 (246 mg, 1.16 mmol). This mixture was stirred for 16 h at r.L, then 5 % NaHCOs (30 ml) was added with vigorous stirring and the mixture extracted twice with EtOAc (50 ml). The organic phases were washed with saturates NaCl solution then dried, filtered and evaporated to afford the crude product which was converted to its hydrochloride salt and purified by reversed phase preparative HPLC using a Nucleosil (Machery-Nagel) N-protected column (20 x50 mm) and an MeCN/water (0.1 % TFA) gradient After pooling and evaporation of the product fractions the title compound was obtained as a white solid (217 mg, 59 % yield), MS: m/e=444.4 (M+H1"). Following the general method of example 83, die compounds of examples 84 to 89 were prepared Example 84 N-f4-Memoxy-7-phenyl-hfmzothiazol-2-yl)-4-pipm hydrochloride salt (1:1) Using piperidine the title compound was obtained as a light yellow solid (78 % yield), MS: m/e=458.4 (M+rT). Example 85 N-(4-Methoxy-7-phenyi-bpn 7nt>iiazol-2-yn-4-niorpholin-4-,\dmethy1-^wiMmi da hydrochloride salt (1:1) Using morpholine the title compound was obtained as a light yellow solid (23 % yield), MS:m/c=460.5(M+Ht). Example 86 4-Diethvlammomemvl-N-f4-mei^oxv-7-phenvi-benzotiu^zol-2-^)-beii2amide hydrochloride (1:1) Using diethylamine the title compound was obtained as a white solid (39 % yield), MS: m/e=446.3 (M+H+). Example 87 N-(4-Methoxy-7-phenvl-bfin2otl]iazol-2-yi)^r(me& methyl]-benzamide hydrochloride salt (1:2) Using 3-(memykminomefliyl)-pyridine the title compound was obtained as a Iigth yellow solid (15 % yield), MS: m/e=495.2 (M+If). Example 88 N- i 4-Methoxv-7-phen,yI-beny.nfhia7r)l-2-yD-4-(4-meth"yl-piperazin-1 -ylmethyi)-benzamide hydrochloride salt f 1:2) Using N-methyl-piperazine the title compound was obtained as a white solid (21 % yield), MS: m/e=473.3 (M+fT). Example 89 4r-Pimethylaminome&yl-Kf-(4-rBellioxy-7-phenvi-benznthia7o1-?.-y1)-hpn7aiTi^Hf-hydrochloride salt (1:1) Using dimediyiamine hydrochloride the title compound was obtained as a light yeflow solid (21 % yield), MS: m/e=418.3 (M+H). Example 90 4-Kf hylaTnin ometfavI-N-("4-methoxy-7-phenvl-benzothia2ol-2-vl 1-benzamide hydrochloride salt f 1:1) To a solution of 4-bromomemyl-N-(4-methox7-7-phenyl-benzotiiiazol-2-yi)-benzamide (300 nig, 0.66 mmol) in THF (2 ml) was added ethylamine (2N in THF) (3 ml, 6.6 mmol) and the mixture stirred at 20 °C for 18 h. The reaction mixture was then evaporated to dryness and the residue treated with an excess of 5N HO/EtOH (3 ml), the ethanol was then evporated and the residue dissolved in DMSO and then subjected to preparative reversed phase HPLC purification using a C18 ODS-AQ column (20x50 mm), eluting with a gradient of MeCN/water (0.1% TFA). The product fractions were pooled and evaporated to afford the title compound as a light yellow solid (238 mg, 79 % yield), MS: m/e=418-3 (M+H+). Following the general method of example 90, the compounds of examples 91 to 126 were prepared Example 91 4-rf2-Memoxy-emv1amino)-memYl1-N-(4-methoxy-7-pheriYl-benzot>iia7j>l-2-v1)-benzamide hydrochloride salt (1:11 Using 2-metboxyethylarnine in dioxane at 90 °C the tide compound was obtained as a light yellow solid (.66 % yield), MS: m/e=448.3 (M+H+). Example 92 4-[(2-Hydroxy-ethvlaminn1-memYl1-N-f4-methoxv-7-phenYl-benzolhiazol-2-yl1-benzamide hydrochloride salt (1:11 Using ethanolamine in dioxane at 90 °C the title compound was obtained as a light yellow solid (68 % yield), MS: m/e=434.4 (M+H). Example 93 4-(Benzykmino-methyl1-N- (4-methoxy-7-phenyI-ben7othiazol-2--yl )-hpn?ami cfc hydrochloride sart i1:\1 Using benzylamine in dioxane at 90 °C the title compound was obtained as a white solid (50 % yield), MSi m/e==48Q3 (M+lT)- Example 94 4-[fBenzyi-methyl-aromoUmethyll-N-(,4-memoxv-7-phenyl-ben7.othia7ol-2--yl)-bertzamide hydrochloride salt d:11 Using N-methyl-benzylamine in dioxane at 90 "C the title compound was obtained as a white solid (74 % yield), MS: m/e=494.3 (M+lT). Example 95 4- f f 3-Imidazol- 1-yl-prnpvl amino ,)-methyI1 -N-(4-memoxy-7-phenvl-beiizothiazol-2-yI1-benzamide hydrochloride salt f 1:21 Using l-(3-arninopropyl J-imidazole in dioxane at 90 °C the title compound was obtained as a pale yellow solid (58 % yield), MS: m/e=498.2 (M+H). Example 96 N-f4-Me&oxv-7-phenvl-ben2othiazol-2-yl)-4-Ufpyric^ benzamide hydrochloride salt (1:21 Using 4-(aminomethyl)-pyridine in dioxane at 90 °C the title compound was obtained as a beige solid (33 % yield), MS: m/e=481.2 (M+H+). Example 97 4-{f(2-Memoxy-emvI1-meiiivl-amino1-me1h^ yl)-ben7flmTHp hydrochloride salt (1:1) Using N-(2-memoxyethyl)-methylarnine in dioxane at 90 °C the title compound was obtained as a light yellow solid (73 % yield), MS: m/e=462.3 (M+H). Example 98 4- (1.1 -Dioxo^-tbiomoroho1in-4-ylme&y0-N-(4-mem^ benzamide hydrocblorde salt ("1:11 To a solution of N-(4-methoxy-7-phenyl-ben^othiazol-2-yl)-4-miomorpholm-4-yUiiethyl-benzamide (350 mg, 0.73 mmol) in CH2C12 (10 ml) was added 3-phenyl-2-(phenylsuifonyl) oxaziridine (288 mg, 1.1 mmol) and the mixture stirred for 2 h at r.L The reaction mixture was then evaporated to drynesss, the residue suspended in ether, and the solid filtered off and washed with ether followed by acetone. This solid was dissolved in methanol (10 ml) and treated with 5N HQ/MeOH for 1 h at rx, the resulting precipitate was filtered off, washed with methanol and finally dried under vacuum (0.05 mmHg, 60 °C) to afford the title compound as a white solid (270 mg, 68 % yield), MS: m/e=508.3 (M+H+). Example 99 N- (4-M^o^-7-phen?l-henzothiazol-2-^)^thiomorphohn-4-vlTTi et>iyl-b Using thiomorpholine in dioxane at 90 "C the title compound was obtained as a yellow solid (68 % yield), MS: m/e=476.1 (M+rf). Example 100 A-TmiHarol-1 -ylniethyl-N-(4-melhoxy-7-phen^-benzothia7n1-2"yI")-benzanTide hydrochloride salt (1:1) Using imidazole in DMF at 90 °C the title compound was obtained as a pale yellow solid (92 % yield), MS: m/e=441.3 (M+FT). Example 101 4-(2-Hvdroxymethyl-imidazol- l-ybnethyD-rj"- (4-methoxy-7-phenyi-benzothiazol-2-ylV benzamide Using 2-hydroxymethyl-imidazole in DMF at 90 °C the title compound was obtained as a pale yellow solid (16 % yield), MS: m/e=471.1 (M+H). Example 102 N-f 4-Methoxy-7-pheny1-bpn7otniazol-2-yD-4- (2-methvli-mifla7y.l-l -yimethyll-benzamide Using 2-methyl-imidazole in DMF at 90 °C the title compound was obtained as a white solid (79 % yield), MS: m/e=455.5 (M+Ff). Example 103 4- (4,5-Dir"^tbyl -iirndazol-1-ylmethvl) -N-f 4-memo:gy-7-phenyl-ben^OthiaZol-2-y^")-hpT]7.armHp Using 4,5-dimethyl-imidazole in DMF at 90 °C the title compound was obtained as a pale yellow solkL (67 % yidd)TMSim/e=469.2 (M+HT)- Example 104 N- (4-Methoxv-7-phenyl-ben2Qihiazol-2-yl"l-4-pipera2dn--1 -vimethvl-benzamide hydrochloride salt f 1:2) Using 1-tert-butoxycarbonyl-pjperazine in dioxane at 90 °C the title compound was obtained as a pale yellow solid (80 % yield), MS: m/e=459.5 (M+H). Example 105 4-AHvlammomethyl"N-(4-methoxy-7-phenyl-beiH;otIn^zol-2-vl)-benzamide hydrochloride salt f 1:1) Using allylamine in dioxane at 90 °C the tide compound was obtained as a pale yellow solid (65 % yield), MS: m/e=430.5 (M+lT). Example 106 H-(4-Metfaoxv-7-phenyl-benzotHazol-2-yl)-4-propyTaminnmemyl-benzar]n^e hydrochloride salt (1:1.) Using propylamine in dioxane at 90 °C the tide compoimd was obtained as a pale yellow solid (63 % yield), MS: m/e=432.4 (M+W). Example 107 N-(4-Metho:xy-7-phenYl-beiizothiazol-2-yl^ bpny^TTuMe hydrochloride salt (1:2) Using 3-(aminomemyl)-pyridine ia THF at 65 °C the tide compound was obtained as a pale yellow solid (28 % yield), MS: m/e=481.3 (M+H+). Example 108 4-f4-Hyd^oxy-piperiHin-1-y1.aelhyl)-N- Using 4-hydioxy-pq>eridine in THF at 65 "C the title compound was obtained as a white solid (61 % yield), MS: m/e=474.3 (M+H). Example 109 4- (3( S)-Hydroxy-pyirolidin- l-vimethvD-N-f 4-metnoxv-7-phenvI-benzothiazol-2-yl)-benzamide hydrochloride salt (1:1) Using (S)-3-hydroxy-pyrrob"dine in THF at 65 °C the title compound was obtained as a white solid (74 % yield), MS: m/e=460.3 (M+H"""). Example 110 4- T1,41 Diazepan-1 -yunethyl-N-f 4-methoxy- 7-phenvl-benzothiazol-2-yl)-benzamide hydrochloride salt f1:2) Using tert-butyl-l-homopiperazine carboxyiate in THF at 65 "C the title compound was obtained as a light yellow solid (87 % yield), MS: m/e=473.2 (M+H). Example 111 4-f 3 ( R)-Dim ptbyl amfno-pyrrolidin- 1-vlmethyl) -N- f 4-methoxv-7-phenyi-benzothiazol-2-yl)-benzamide hydrochloride salt (1:2) Using (3R)-(+)-3-dimethylamino-pyrolidine in THF at 65 °C the title compound was obtained as a light brown solid (51 % yield), MS: m/e=487.3 (M+H). Example 112 N-f 4-Methoxy-7-phenyI-benzothiazol-2-vD-4-1 (2-morpholm-4--^-ethv1amino)-methvl ] -benzamide hydrochloride salt (1:2) Using 4-(2-aminoethyl)-morpholine in THF at 65 °C the title compound was obtained as a light yellow solid (44 % yield), MS: m/e=503.3 (M+H). Example 113 N-(4-Methoxv-7-phenvi-bfflzothiazol-2-yl)^r(2^ benzamide hydrochloride salt (1:2) Using N-(2-aminoethyl)-pyrrolidme in THF at 65 °C the title compound was obtained as a light yellow solid (37 % yield), MS: m/e=487.3 (M+H). Example 114 N-(4-MethoxY-7-phenyI4ienzothiazoI-2-vD^rf2-piperi bemamide hydrochloride salt {1:2) Using N-(2-aminoetiayl)-piperidinee in THF at 65 °C the tide compound was obtained as a ! light yellow solid (50 % yield), MS: m/e=501.3 (M+H). Example 115 4-Cvdobutykmmomelhyl^N-f4~memoxv-7-phenyl-ben7^thia7ol-2-yl")-bf,n7jm;Hp. hydrochloride salt (1:1) Using cyclobutyiamine in THF at 65 °C the title compoimd was obtained as a white solid i (68 % yield), MS: m/e=444.3 (M+lT). Example 116 4-Cydopentyiammomediyl-N-l"4-methoxy~7-phenyl-benzofliiazol-2-vl 1 -bgn7.amiH p hydrochloride salt f 1:1) Using cyclopentylamine in THF at 65 °C the title compound was obtained as a light biown solid (46 % yield), MS: m/e=458.4 (M+H). Example 117 4-{[(Furan-2-ylmemyl)-aipmo1-memvU-N-(4^ benzaroide hydrochloride salt (1:1) Using 2-(aminomediyl)-furan in THF at 65 °C the title compound was obtained as a beige solid (57 % yield), MS: m/e=470.2 (M+H). Example 118 N-(4-Methoxr-7-phmYl-hqm>ihiazol-2-Yl)-4-W benzamide hydrochloride salt (1:1) Using 2-(aminomethyi)-djiophene in THF at 65 °C the title compound was obtained as a light yellow solid (60 % yield), MS: m/e=486.3 (M+H). Example 119 4-Diprop^aininomediyl-N-f4-methoxv-7-phen^-benzothiazol-2-^"l-benzamide hydrochloride salt (1:1) Using dipropyiamine in THF at 65 °C the tide compound was obtained as a white solid (64 % yield), MS: m/e=474.3 (M+H). Example 120 N-f4-MethoCT-7-phenyi-benzodiiazoI-2-yl)^U methyil-"henzamide hydrochloride salt (1:21 Using 2-[(2-(meth)damino)ethyi]-pyridine in THF at 65 °C the tide compound was obtained as a beige solid (46 % yield), MS: m/e=509.3 (M+H). Example 121 4-AmmomeraYl-N-f4-metfao:^-7-phenvi-benzothiazol^ salt f 1:1) Using ammonia (7N in MeOH) in THF at 20 °C the tide compound was obtained (after 4 days) as a white solid (34 % yield), MS: m/e=3891 (M). Example 122 4-1 (CyclopTQP^methvI-amino)-memyl1 -N-(4-memoxy-7-phenyi-ben7.ntinazol-2-vl)-henramide hydrochloride salt (1:1) Using aminomethyl-cyclopropane in dioxane at 90 °C the title compound was obtained as a light yellow solid (69 % yield), MS: m/e=444.3 (M+H+). Example 123 N-(4-MethoxY-7-phenvi-beiizothiazol-2-vl)-^ benzamide hydrochlorde salt (1:2) Using 2-(methyldiio)-ediylamine in THF at 65 °C the title compound was obtained as a light ydlow solid (74 % yield), MS: m/e=464.2 (M+H1"). Example 124 N-(4-Memoxv-7-phenvl-benzotniazol-2-yl)-4-tniazoBdm^ bvrirorfflordeaak(l:l) Using thiazolidine in THF at 65 °C the title compound was obtained as a white solid (48 % yield), MS: m/e=462.2 (M+H). Example 125 4-(3(S)-Dimrthylarnmo^pvrroKdm-l-yimethv^^ yQ-benzamide hvdrochiorde salt (la) Using (3S)-(-)-3-(dmiemylaniino)-pyrroIidine in THF at 65 °C the title compound was obtained as a light brown solid (56 % yield), MS: m/e=4S7.3 (M+H). Example 126 4-ff2-DJinrthy1aTniiio-ethy]aminoymrthvl1-N-f4^ benzamide hydrochloride salt (1:2) Using 2-{dmiethylamino)-ethylamine in THF at 65 °C the title compound was obtained as a light yellow solid (32 % yield), MS: m/e=461.3 (M+ H). Preparation of the 4-0R1R2-ammo)-N-(4-methoxy-7-ai7l-ben2othiazol-2-yl)-benzainides: General Procedure G The appropriate 2-amino--7-aryl-4-methoxy-benzothiazol is converted with 4-(chloromethyl)ben2oyl chloride using the general method of example 1. The product is then converted neat with the appropriate amine (10 equivalents) at 100 "C for 24 hours. The reaction mixture is then dissolved in ethyl acetate, extracted with water and brine, dried and evaporated in vacuo. Flash chromatography (silica, eluent dichloromethane containing 1.2 to 2.4 % methanol) affords the product in about 50 % yield. Example 127 4-Qoromethyl-N-("4-me&oxy-7-niorp]M^ and 2-ammo-4-methoxy-7-morphoIin-4-yi-benzomiazol (1-0 g, 3.8 mmol), 4-(chloromethyi) benzoyl chloride (810 mg, 4.2 mmol) and pyridine (036 ml, 4.5 mmol) are reacted in dichloromethane (20 ml) for 18 h. The reaction is quenched with water (25 ml) and brought to pH 8.0 with sodium carbonate. The mixture is extracted with dichloromethane and the combined organic layers are dried and evapoarted to dryness. Flash chromatography (silica, eluent methylene chloride containing 2.5 % methanol) affords the product as white crystalls in 54 % yield. MS: m/e= 418 (M+H"). FoJhwingthe general method the compounds of examples 128 to 132 were prepared Example 128 4-f4-HYdroy^-piperidm-l-vlmemyl)-N-(4-memoxy-7-morpholm^-yl-benzothiazol-2-vlVbenzamide Ojnverdonof4KJoromethyi-N-(4-memoxy-7-morpholm^yi-benzothia2»l-2-yi)-benzamide (&4 mg, 0.20 mmol) -with 4-b-ydroxypipeia2m (200 mg, 2.0 mmol) using lie general procedure C affords the product as white solid in 73% yield. MS: m/e= 483 (M+H+). Example 129 4-S [ (2-Methoxv-etfaylVmethvl-amino] -meth"vi}-N-(4-methoxv-7-morpholin-4-yl- benzothiazol-2-vl")-beiizamide Conversion of 4^oromethyl-N-(4-methoxy-7-morpholm-4-yl-benzothiazol-2-yi)- benzamide (84 mg, 0.20 mmol) with N-(2-memoxyemyl)-memylarmn (178 mg, 2.0 mmol) using the general procedure C affords the product as white solid in 55% yield. MS: m/e= 471 (M+H). Example 130 4~f f (2-Hvdroxy-ethyI)-methyi-amino ] -methyl ?-N-(4-metnoxy- 7-morphoiin-4-yi-ben2othiazol-2-yl)-benzamide 3,4-Dimethoxy-benzoic add 2-{[4-(4-memoxy-7-morpholm-4-yl-benzothiazol-2-yl carbamoyl)- benzyl] -methyl-amino}-ethyl ester (63 mg, 0.10 mmol) are heated in aqueous sodium hydroxide (1M, 0.5 ml) and ethanol (2 ml) to 100 °C for 30 min The mixture is diluted with water and extracted twice with ethyl acetate. The combined organic layers are extracted with saturated aqueous sodium hydrogencarbonate, dried and evaporated to dryness. Flash chromatography (silica, eluent methylene chloride containing 5 % methanol) affords the product as white crystals in 48 % yield. MS: ra/e= 457 (M+H). Example 131 3,4-Dimethoxv-benzoic acid 2-{f4-(4-methoxv-7-morph,nli"-^-Yl-benzothiazol-2-yicarb^mr.yl)- hfri7yl\|-methyl-a™"nol-ethyl ester Q3nveraonof4-dorome1iiyl-N-(4-memoxy-7-morpholm-4-yI-benzothiazol-2-yl)-benzHnnVfe (84 nig; (K2fr rmnof^ with 3,4-£m.dthvxywiixoiC JCKT 2-merhyIaximio;-eth"yI ester chlorohydrate (96 mg, 0.4 mmol) and N-ethyl diisopropyiarnine (0.14 ml, 0.80 mmol) using the general procedure C affords the product as light yellow solid in 57% yield. MS:m/e=621(M+lT). Example 132 N-f 4-Memory-7-morphoIm-4-yl-berizothiazol-2-yi)-4-pipera2in-1 -ylmethyi-benzamide Conversion of 4-doromemyl-N-(4-memoxy-7-morpholm-4-yl-benzothiazol-2-yl)-benzamide (84 mg» 0.20 mmol) with 1-BOC-piperazine (372 mg, 1.9 mmol) using the general procedure C and afterwards cleavage of the neat carbamate in trifluoroacetic acid (1 ml) followed by saturated aqueous sodium carbonate affords the product as colorless crystals in 72% yield. MS: m/e= 468 (M+H). Example 133 N-(7-Ben2^oxp-4-methoxv-benzothiazol-2-yl)-4-chloromeaSYl-hf?ny.arniH^ Following the general method of example 1 the title compound was obtained as a light yellow solid (70 % yield). MS (EI): me/e = 438 (M). Example 134 N- f 7-Benzvloxy-4-memoxy-hen7nthiazol-2-yl)-4~( ^-Himethylamino-pyrroUdm-1-vtmethyi)-^"?an-nde hydrochloride According to general procedure C the title compound was obtained as a light brown solid (86 % yieId)..M.p.: 195° C (dec). Preparation of the 3^f7-arvi^methoxy-benzothiazol-2-yl)-l--R3-l-R General procedure D: The appropriate 2-arnino-7--aryi-4-methoxy-benzothiazol (1 part) and pyridine (1.2 equivalents) are dissolved in 40 parts tetrahydrofuran and treated with phosgene (20 % in toluene, 1 equivalent) at ambient temperature. After 60 min, the reaction mixture is concentrated to half the volume under reduced pressure and the appropriate amine (1.25 equivalents) and pyridine (1.1 equivalents) are added. After 15 min at ambient temperature, the reaction mixture is evaporated to dryness. The product is isolated by flash chromatography (silica, eluent dichloromethane containing 2.5 % methanol). FoUowingthe general method the compounds of examples 135 to 137 were prepared Example 135 Tbiomorpholine-4-cafboxylic acid f4-memoxy-7-morpholm-4-yl-benzotfaiato]-2-yl)-amide Conversion of 2-andno-4-methoxy-7-morpholin-4-yl-ben2otbia2ol (100 mg, 0.377 mg) with phosgene (20 % in toluene, 0.2 ml) and thiomorpholine (0.045 ml, 0.47 mmol) using the genera] procedure D affords the product as white solid in 73 % yield. MS: m/e= 395 (M+H+). Example 136 Morpholine-4-carboxylic acid (4-methoxy-7-morphoIm^-yl-benzothia2oI-2-viVamide Conversion of 2-amino-4-methoxy-7-morpholin-4-yl-benzo&iazol (100 mg, 0.377 mg) with phosgene (20% in toluene, 0.2 ml) and morpholine (0.041 ml, 0.47 mmol) using the general procedure D affords the product as white solid in 25 % yield. MS: m/e= 379 Example 137 3- f 4-Methoxy-7-mor^holin-4-yl-benzothiazoi-2-vlV 1-methyl-1 -(6-methyl-pvridin-3-yimethvD-urea Conversion of 2-amino^-methoxy-7-morpholm^yl-benzothiazol (100 mg, 0.377 mg) with phosgene (20 % in toluene, 0.2 ml) and memyl-(6-merhyl-pyridm-3-ylmemyl)-aniine (0.064 ml, 0.47 mmol) using the general procedure D affords the product as white solid in 25 % yield. MS: m/e= 429 (M+H+). Example 138 l-Furan-2-yi-memvl"3-(4-me^oxy"benzothiazol-2-,vi")-urea To a solution of (4-Methoxy-benzothia2ol-2-yl)-carbamic acid tert-butyl ester (80 mg> 0.29 mmol) in dioxane (2 ml) was addded furfiirylamine (55 mg, 0.57 mmol) and the mixture heated to 100 °C for 20 h. The reaction mixture was then evaporated to dryness and the residue recrystallised from ether/nHexane to afford the title compound as a beige solid (80 mg, 92% yield), MS: m/e=303 (M). Following the general method of example 138, the compounds of examples 139 to 163 were prepared Example 139 1 -Furan-2-vi-methyl-3- (-4-methoxy-7-phen^-benzothiazol-2-yl)-urea * Using (4-Methoxy-benzothiazol-2-yl)--carbamic acid tert-butyl ester and forfiirylamine the title compound was obtained as abeige solid (66 % yield), MS: m/e=380.3 (M+H+). Example 140 l-(4-Me&oxy-7-phen^d-benzo1faiazol-2^)-3-thiophen-2-yl-methvl-urea Using (4-methoxy-7-phenyl-ben2oyhiazol-2-yl)-carbamic acid tert-butyl ester and " tIriophene-2-methyiamine the title compound was obtained as a beige solid (62 % yield), MS: m/e=396.3 (M+JT). Example 141 l-(4-Memoxy-7-phenyl-ben20tlmzol-2-yl)-3-pvridin--2-vl-methyl-urea Using (4-methoxy-7-phenyl-benzoyhia2ol-2-yl)-carbamic acid tert-butyl ester and 2-(aminomethyl)-pyridine the tide compoundwas obtained as a beige solid (18 % yield) following purification using reversed-phase preparative HPLC C18 ODS-AQ, with an MeCN/ water gradient, MS: m/e=391.2 (M+H+). Example 142 l-f4-Methoxv-7-phenyl-beri2othiazoI-2-yl)-3-pyrTHin-3-^mf-thYl-i]rea Using (4-methoxy-7-phenyl-benzoyhiazol-2-yl)-carbamic acid tert-butyl ester and 3-(aminomethyl)-pyridine the tide compound was obtained as abeige solid (18 % yield) following purification using reversed-phase preparatie HPLC, CI 8 ODS-AQ, with a water/acetonitrile gradient, MS: m/e=391.2 (M+Ef). Example 143 l-(4-Memo:xT-7-phenyl-berizo1hiazol-2-yl)-3-pTO Using (4-metnoxy-7-phenyl-ben2»yhiazol-2-yl)-carbamic acid tert-butyl ester and 4-(aminomethyl)-pyridine the tide compound was obtained as a beige solid (52 % yield), MS:m/e=391^(M+lT). Example 144 3-f4-Memo:%y-7-phenyl-benzolliiazol-2-vl)-l-meth^ Using (4-methoxy-7-phenyl-ben2oyhia2ol-2-yl)-carbamic add tert-butyl ester and 3-(methylaniinomethyl)-pyridine the title compound was obtained as a bdge solid (23 % yield), MS: m/e=405.4 (M+H). Example 145 1 - C4-Methoxv-7-phemyl>benzothiazol-2-vl)--3-phenetbyl-urea Using (4-methoxy-7-phenyl-ben2oyhiazol-2-yl)-carbainic add tert-butyl ester and pbenethylamine the title compound was obtained as a beige solid (77 % yield), MS: m/e=404.5 (M+H). Example 146 l"f4-Methoxy-7-phenyl-benzotbia2ol"2-yl")-3-(3-phenyl-propyl)-urea Using (4-metboxy-7-phenyl-benzoyhiazol-2-yl)-carbamic add tert-butyl ester and 3-phenyl-propylamine the title compound was obtained as a beige solid (71 % yield), MS: m/e=4173 (M+H). Example 147 l-f4-Memoxy-ben^)-3-(4-metboxy-7-phenyl-benzothiazol-2-vl)-urea Using (4-methoxy-7-pnenyl-benzoyhiazol-2-yl)-carbamic add tert-butyl ester and 4-methoxy-benzykmine the title compound was obtained as a beige solid (60 % yield), MS: m/e=420.3 (M+H). Example 148 3,4-Dihydro-lH-isoquinoline-2-carboxyiic add (4-metfaoxv-7-phenyl-ben2otbiazol-2-yl)-amide Using (4-me1noxy-7-phenyl-benzoyhiazol-2-yl)-carbamic add tert-butyi ester and 1,23J4-tetrahydroisoquinoline die title compound was obtained as a beige solid (31 % yield) following purification using reverse-phase prep. HPLC, C18 ODS-AQ, with a water/acetonitrile gradient, MS: m/e=416.3 (M+H1"). Example 149 I - (2-Dunethviamino-ethyO-3-(4-methoxy-7-phenvi-benzothiazol-2-yi)-urea Using (4-methoxy-7-phenyl-benzoymazo]-2-yl)-carbamic acid tert-butyl ester and 2-dimethylamino-ethylamine the title compound was obtained as a beige solid (67 % yield), MS:m/e=371.3(M+H+). Example 150 1 - (2-Hvdjoxy-ethylV3-f 4-methoxy-7-phenylrbenzothiazol-2-yl)-urea Using (4-methoxy-7-phenyi-benzoybiazol-2-yl)-caibamic acid tert-butyl ester and ethanolamine the title compound was obtained as a beige solid (35 % yield), MS: m/e=344.3 (M+H+). Example 151 1 - (4-Methoxy-7-phenyl-benzothiazol-2-vI1-3-( 2-piperidin-l-yi-ethyH-urea Using (4-methoxy-7-phenyl-benzoyhiazol-2-yi)-carbamic acid tert-butyl ester and l-(2-aminoethyl)-piperidme the title compound was obtained as a beige solid (67 % yield), MS: m/e=411.4(M+H+). Example 152 l-f4-Me&oxv-7-phenyl-berizolhia2ol-2-ylV3-{2-morpbolm^vi-elfayiVurea Using (4r-methoxy-7-phenyi-benzoyhiazol-2-yi)-carbarnic acid tert-butyl ester and 4-(2-ammoethyl)-morpholine the title compound was obtained as a beige solid (29 % yield), MS:m/e=413.4(M+rD. Example 153 I- f 4-Methoxv- 7-phenvl-benzothia7.nI-3-vl )-3-f 2-pyridin-2-vi-ethyD-urea Using (4-rnethoxy-7-phenyl-benzoyhiazol-2-yl)-carbamic acid tert-butyl ester and 2-(2-aminoethyl) -pyridine the title compound was obtained as a beige solid (88 % yield), MS: m/e=405.4 (M+H). Example 154 i-r^-Tmidazol-l-yl-propyl)-3-(4-Tnethoxv-7-phenyl-bfin7rttliia7nl-2-ylVurea hydrochloride salt (1:11 Using (4-methoxy-7-phenyl-ben2»yhiazol-2-yl)-caibamic acid tert-butyl ester and N-(3-aminopropyl)-iniidazole the free base was obtained which was was treated with 5N HCl/EtOH followed by crystallisation from methanol/ether to afford the titie compound as a beige solid (72 % yield), MS: m/e=408.3 (M+-H). Example 155 l-Ethrl-3-(4-memoxy-7-phenyl-benzothi^ hydrochloride salt f 1:1) Using (4-methoxy-7-phenyl-benzoyhiazol-2-yl)-carbamic acid tert-butyl ester and4-(N-emylaminomethyl)-pyridine the free base was obtained which was was treated with 5N HCl/EtOH followed by crystallisation from acetonitrile to afford the titie compound as a white solid (64 % yield), MS: m/e=419.3 (M+H). Example 156 l-f2-Imid^oI-l-yl-emYl)-3-(4-memoxy-7-phenyl-benzothiazol-2-vl>-ureahydrocM salt f 1:1) Using (4-methoxy-7-phenyi-ben2oyhia2ol-2-yl)-carbamic acid tert-butyl ester and N-(2-ammoemyl)-imidazole the free base was obtained which was was treated with 5N HCl/EtOH followed by crystallisation from a Example 157 Morpholine-4-carboxylic acid f4-methoxy-7-phenyl-benzothiazoI-2-yl)-aTnide Using (4-methoxy-7-phenyl-benzoyhiazol-2-yl)-caibamic add tert-butyl ester and morpholine the the title compound was obtained as a white solid, following crystallisation from ether/ nHexane (67 % yield), MS: m/e=370.3 (M+rT) Example 158 Thiomorpholine-4-carboxyUc acid (4-methoxy-7-phenyl-ben2otbiazol-2-vl")-amide Using (4-methoxy-7-phenyl-benzoyhiazol-2-yl)-carbamic acid tert-butyl ester and thiomorpholine the the title compound was obtained as a white solid, following crystallisation from ether/nHexane (88 % yield), MS: m/e=386.2 (M+H). Example 159 1-Oxo-ll 4-diiomorphfi1inp-4-carboxvhc acid (4-methoxy-7-phenvl-benzothia2ol-2-yD-amide To a solution of thiomorpholine-4-carboxylic acid (4-methoxy-7-phenyl-benzothiazol-2-yl)-amide (240 mg, 0.62 mmol) in CH2CI2 (10 ml) was added 3-phenyi-2-(phenylsulfonyl) oxaziridme (244 mg, 0.92 mmol) and the mixture stirred for 2 h at r.L The solvent was then reduced to ca. 2 ml and the mixture ultrasonnicated for 15 min. with addition of ether (10 ml). The solid precipitated was filtered off, then dried under vacuum (0.05 mmHg, 60 °C) to afford the tide compoundas a light yellow solid (90 % yield), MS: m/e=402.9 (M+if). Example 160 !-[2-(lJ-IMoxo-ll6-tMomorpholm^vlVethvI1-3-f4-medioxy-7-pheiiyl-benzothiazol-2-yD-urea hydrochloride (1:1) Using (4-meliioxy-7-phenyl-ben2oyhia2ol-2-yl)-carbaniic acid tert-butyl ester 2-(l,l-Dioxo-tmomorpholin-4-yl)-emyIainine the free base was obtained, which was converted to the hydrochloride salt by treatment with 5N HQ/EtOH followed by under vacuum (0.05 mmHg, 60 °C) to afford the title compound as a beige solid (87 % yield), MS: m/e=4612 (M+rT). Example 161 3- f 4-Methoxy-7-phenyi-ben2othi azol-2-yIV 1 -methvl-l-(6-roedivl-pyridin-3-yI-memyl")-urea hydrochloride salt (1:2) Using (4-methoxy-7-phenyl-benzoyhiazol-2-yl)-carbamic acid tert-butyl ester and metiiyl-(6-memyI-pyridm-3-ylmethyl)-amhie, the free base was obtained, which was converted to the hydrochloride salt by treatment with 5N HQ/EtOH followed by recrystallisation from acetonitrile then drying under vacuum (0.05 mmHg, 60 °C) to afford the tide compound as a white solid (61 % yield), MS: m/e=448.9 (M+H+). Example 162 3-(4-Methoxv-7-phenyl-benzotbiazol-2-yl)-l -mefliyl-l-pyriHin -7-yl-methvl-urea hydrochloride salt (1:2) Using (4-methoxy-7-phenyl-benzayhiazoI-2-yl)-carbamic acid tert-butyl ester and methyl-pyridin-2-yl-mediyl-amine, the free base was obtained, which was converted to the hydrochloride salt by treatment with 5N HCl/EtOH followed by recrystaffisation from EtOH/ether then drying under vacuum (0.05 romHg, 60 °C) to afford the title compound as a white solid (70 % yield), MS: m/e=494.4 (M+H+). Example 163 3-j4-Methoxy-7-phenyI-benzothiazol-2-yl) - l-methyl-1 -pvridin-4-vi-methvi-urea hydrochloride salt (1:2^ Using (4-methoxy-7-phenyl-berizoyhia2ol-2-yi)-carbamic acid tert-butyi ester methyi-pyridin-4-ylmethyl-arnine the free base was obtained, which was converted to the hydrochloride salt by treatment with 5N HCl/EtOH followed by recrvstaflisation from EtOH/ether then drying under vacuum (0.05 mmHg, 60 °C) to afford the title compound as a white solid (65 % yield), MS: m/e=480.3 (M+fcT). Example 164 3-(4-Methoxv-7-phenyl-benzotliia2ol-2-vI)-l-met^^ To an ice cooled solution of 3-(4-memoxy~7-phenyl-benzotluazol-2-yl)-l-methyl-l-pyridin-3-yl-methyl-urea (405 mg, 1 mmol), in CH2CI2 was added 3-chloro-perbenzoicadd (MCPBA) (295 mg, 1.2 mmol) and the mixture stirred at 0 °C for Ih, followed by 1 h at r.t After this time the pale red reaction mixture was thoroughly washed with 5% NaHC03 solution (50 ml), and the aqueous phase was extracted with CH2G2 (2x 30 ml) then the combined extracts were dried with Na^CU, filtered and evaporated to affording a violet solid. This solid was then chromatographed over SiCh (Merck 230-400 mesh) during with a gradient of CH2a2/(2N NHj/MeOH) (97:3 to 9:1), to afford the tile compound as a light brown solid (260 mg, 62 % yield),MS". m/e=421.3 (M+H) Example 165 l-Benzvl-3-f4-methoxy-benzothiazol-2-vl)-urea To a stirred solution of 2-amino-4-methoxy--ben2othiazole (180 mg, 1 mol) in THF (5 ml) was added benzylisocyanate (166 mg, 1.25 mmol) and the mixture heated to 60 °C for 3 h. After evaporation of the solvent, ether (5 ml) was added and the suspension ultra-sonnicated for 10 min with addition of nHexane (5 ml). This suspension was filtered and washed further with ether/nHexane (1:1) to afford the title compound, after drying under vacuum, as a white solid (220 mg, 70 % yield), MS: m/e=313 (M). Following the general method ofexample 165, the compound of example 166 was prepared Example 166 l-Berizvl-S-f^metnoxy-y-phen^-berizothiazoI^-^Vurea Using 2-ammo-4-memoxy-7-phenyi-benzothiazoIe the title compound was obtained as a white amorphous solid (92 % yield), MS: m/e=389 (M) Example 167 1 - f 4-Methoxy-7-phenvi-benzntliia7.pl -2-yl)-3-pyriHin-Vyl-thi nnrea To a stirred solution of 2-arnmcK4-methoxy-7-phenyl-benzothiazole (80 mg, 0.3 mmol) in dioxane (3 ml) was added pyridine-3-isothiocyanate (64 mg, 0.47 mmol) and the mixture heated to 100 °C for 69 h. After cooling to r.t the resulting yellow suspension was filtered, washed with ether (5 ml) and dried under vacuum (0.05 mmHg, 50 °C, to afford the tide compound as a; light yellow solid (98 mg, 80 % yield), MS: m/e=393.1 (M+H+). Example 168 l-Benzoyl-3-f4-methory-7-phenyl-ben2othmol-2-viVthiourea To a suspension of 2-amino-4-methoxy-7-phenyI-benzothiazoIe (1.52 g, 6 mmol) in dioxane (60 ml) was added benzoyusothiocyanate (1.45 g, 8.9 mmol) and the mixture heated to 100 °C for 2 h, during which time the suspension dissolved. After cooling the solvent was removed and the solids suspended in hot acetonkrile (100 ml) and filtered while warm (50 °C). The solid collected was washed with acetonitrile (20 ml) then dried under vacuum (0.05 mmHg), at 60 °C. to afford the tide compound as z pale yellow amorphous solid (1.38 g, 55 % yield), MS: m/e=419.0 (it). Example 169 (4-Methoxy-7-phenyl-benzothiazol-2--vl)-thiourea To a solution of l-benzoyl-3-(4-memoxy-7-phenyl-ben2otiiiazol-2-yi)-thiQurea (13 g, 3.1 mmol) in methanol (20 ml)/THF (40 ml) was added NaOMe (250 mg, 4.6 mmol) and the mixture stirrd for 72 h at r.t. After evaporation of the solvents water (100 ml) was added with stirring followed by aceticacid (1 ml) which caused a solid to precipitate. This solid was collected and on a glass sinter, washed with water (100 ml), followed by EtOAc (30 ml) then finally cyciohexane (30 ml). After drying the tide compound was obtained as a white solid (850 mg, 87 % yield), MS: m/e=316.2 (M+JT). Example 170 (4-Methoxy-beiizothiazol-2-yl)-iirea Amixtureof2-anihio-4-methox7-ben2othiazole(330rag, 1.83 mmol) and urea (1.1 g, 1.83 mmol) were heated together for 1 h at 170 °C, with evolution of ammonia. After allowing to cool to r.t, water (10 ml) was added and the mixture was vigorously stirred. The solid was then filtered, washed, with water (10 ml) followed by ethanol (10 ml) and dried at 60 °C under vaccum (0.05 mmHg). The tide product was afforded as an off-white solid (300 mg, 73 % yield), MS: m/e= 223 (M+). FoUowing the general method of example 170, the compounds of examples 171 to 173 were prepared Example 171 f4-Memoxy-7-phenyl-benzothia20I-2-yI)-urea Using 2-airuno-4-methoxy-7-phenyl-beazotbiazale the title compound was prepared as white solid (58 % yield), MS: m/e= 299 (M+). The preapration of this compound is decribed in the following patent literature; N-(Benzothiazol-2-yl)oxamic acid derivatives. W. Winter, M. Thiel, A. Roesch and O. H. WUhelms, German Patent, DE 2656468,1978. Example 172 f4,6-Difluoro-bep7nthia7nl-2-yl1-urea Using 2-ammo-4J6-difluoro-benzothiazole the title compound was prepared as a light yellow solid (42 % yield), MS: m/e= 229 (M+). Example 173 (7-Isopropyi-4-methaxy-ben2Qtbiazol-2 -yD-urea The title compound is described in the following patent literature and was prepared according to the procedure described therin; N-(Benzothiazol-2-yl)oxamic acid derivatives. W. Winter, M. Thiel, A. Roesch and O. H. Wilhelms, German Patent, DE 2656468,1978. Example 174 (4-Methoxv-7-phenyl-bertzotbiazol-2-yl)-pyric%i-3-yhiiethvl-amine WE CLAIM: 1. Novel benzothiazolc derivatives of formula wherein R1 is hydrogen, Ci.6-alkyl, Ci-s-alkoxy, benzyloxy, cycloalkyloxy, halogen, hydroxy oi tiifluoromethyloxy, R3 is hydrogen, halogen, Q-e-alkyl or Cus-alkyloJcy; R is hydrogen, C^-alkyl, C3-s-aIkenyl, halogen, -C(O)- Q-e-alkyL -C(0)-halogen-Q. s-alkyJ, -CH(OH)-haIogen- Cu-alkyl, -C{0)0-Q^- alkyl, -NHC(O)- C].s-alkyi, -(CH2)n-OH, or is phenyl, which is optionally attached to the benzo group via the linker - (0)m-(CH2)a- and is optionally substituted by N(Rs)(R6), halogen or nitro, or is 2;,3-dihydrQ-lH-indolyl,a2epan-l-yl, [l,4]oxazepan-4-yI, oris a five or six rnembered aromatic or non aromatic heterocyde, which may be attached to the benzo group via the linker - (0)m-(CH2)„ or - N=C(CH3)-and is optionally substituted by one or two group(s) R7, wherein R7 is defined below; with the proviso that Rl, E.3 and R4 are not simultaneously hydrogen, R7 is d.ralkyl, Ce-alkoxy, -C(O)^ Cs-alkj-l, -C(0)Q-ben2yl, -C(0)0- G-s-alkyl, - (CH2)nNR5R6, pyridinyl, optionally substituted by Ci-g-alkyl, or is -CH2N(R5)-C(0)0-Ci-e-aIkyl, -NH-C(phenyI}3, pyrrolidinyl, piperidinyl, morpholmyl or piperazinyl, optionally substituted by Ci.s-alkyl; n is 0, 1,2, 3 or 4; m is 0 Or I; o is 0, 1,2, 3 or 4; and their pharmaceutically acceptable salts, 2. Novel compounds of formula IA according to claim \| wherein R1 is hydrogen, Q-e-alkyl, Q^-alimy, halogen, hydroxy or trifluoromethyioxy; R3 is hydrogen, halogen, C2.6- alkyl or Ci^-alfcyloxy; R4 is hydrogen, d.s-alkyi, halogen, -C(0)OH, -CfO)0- CM-alkyl, -NHC(0)-Ci-6-alkyl, -{CHJJQ-OH, or is phenyl, which is optionally attached to the benzo group via the linker - (0)m-(CH2)„- and is optionally substituted by N(RS)(R6), halogen or nitro; or is a five or six membered aromatic or non aromatic heterocycle, which is attached to the benzo group via the linker - (0)m-(CH2)n and is optionally substituted by Ci-s-alkyl, -C(0)0-benzyl or - NRSR6; with the proviso that R1, RJ and R4 are not simultaneously hydrogen, R" is phenyl, substituted by -C(0)H, or by the following groups -(CH2)nOH with the exception of OH, -(CH2)nN(RE)-(CH2)0- Ci.(r-aIkoxy, -CCH2)nN(R5)-(CH2)D-cycloalkyl, -(CH3)nN(Rs)-(CH2)D-S- Q.s-alkyl, -(CH2)nN(R5)-(CH2)0-phenyI, -{CH2)„N(R5)-(CH2)0OH, -(CH2)nN(R5)-(CH2)0~0-CH(OH)-QH3(OCH3)2, -(CH2)nN(R5)-(CH2)0-O-C(O)-QH3(OCHs)2, -S(0)2-morpholin or is phenyl, which is optionally substituted by -(CKkJn-five to seven rnembered aromatic or non aromatic heterocycle, and wherein the heterocycle may farther substituted by hydroxy, -N(R5)(R6) or Q.s-alkyl; X isOor S; R5, R6are independently from each other hydrogen or Ci-j-aBcyl, n is 0,1,2, 3 or 4; m is 0 or 1; o isO, 1,2, 3 or 4; and their pharrnaceutically acceptable salts, !. The compounds of formula 1A in accordance with claim 1, wherein R1 is methoxy, X is oxygenand R3 is hydrogen. The compounds of formula IA in accordance with claim 3, wherein R" is phenyl, substituted by -CH2OH, -CH:NHCH2CH2OCH3, -eH2NHCHaCH2OH, -CH2NHCH2-pyridinyl, -CH2NH2, -CH2NHCH:CH:SCH3, -CH2N(CH3)CH3CH2SCH3) -CHjN(CH3)CH2CH;OCH3, -CH2N(CH2 CHj)CH2CH2OCH3, -CH2NHCH3, -CH2SCHjCH2N(CH3)2, -CH2OCH3, -CH2OCH2CH2OCHj or -CH:N(CH3)C(0)OCH3. The compounds of formula IA in accordance with claim 4, which compounds are 4-hydroxymethyl-N- (4-methoxy-7-pheny!-benzathiazal-2-yl) -benzamide, yi)-benzamide, 3H((2-m«hory-ethyI)-m«hyl-antiiio]-methyI}-N-(4-methoxy-7-inorpholiii-4-yl- benzothlazol-2-yl) -benzamlde, 4-[(2-^oxy-eth^amino)-methyl]-N-(4-methDy-7-inorpholin-4-yl-ben20thia2ol-2-yl)- benzamide, N-(4-methoKy7-inorpho]in-4-yl-benzothiazoI-2-yl)-4-methylaminonicthyl-benzainide, 4-(2-dimethylainino-ethylsu]fanylrnethyI)-N"-(4-raethaKy-7-morpholin-4-yi- benzotbia2ol-2-yI) -benzamide, 4-{[(2-ethoxy-ethi4)-ediyl-amino]-methyl}-N-(4-methoxy-7-morpholin-4-yI- benzothiaZol-2-yl)-benzamide, 4^f[(2-«iox^-ethyl)-methyl-ainiijo]-meliiyl}-N-(4-methoxj"-7-morpho]in-4-y!- benzothiazoI-2~yl) -benzamide, 4-(2-methoxy-d:hc)xymethyl)-N benzamide, 4-methoxymethyl-N-(4-metho3cy-7-morphoiin-4-yl-benzothia2ol-2-yl)-benzamide, N-(4-merhoxy-7-thiomorpholin-4-yl-benzothiazoI-2-yl)-benzamideand [4-(4-metho^-7-morpholin-4-y]-benzothia2oI-2-ylcarbanioyl)-benzyl]-meth^-catbamic acid methyl aster. 6. The compounds of formula IA in accordance with claim 1, wherein R" is phenyl, substituted by a optionally substituted -(CR^Ja-five to seven membered aromatic or non aromatic heterocycle. 7. The compounds of formula IA in accordance with claim 6, which compounds are 44midazol-l-ylmetiyI-N-(4-methffKy-7-phenyl-beii20thiazol-2-y3)-benzarriide! 4-(4-HychQ^-pipexidin-l-ylmethyt)-N-(4-methoxy-7-phenyl-beriZothiazol-2-yl)- benzamide, 4-[I4]dia2epan-l-y]methyl-N-(4-raethoxy-7-phenyl-ben2othiazol-2-yl!)-benzainicle, 4-(3(S)-dunirthylarmno-pyrroIidin-l-yImethyI)-N-(4-methoxy-7-pheny]-benzothiazol-2- yl)-benzamide, N-{4-methosy-7- f 2- (6-methyl-pyridin-3-yl)-thiai:ol-4->i] -benzothiazol~2 -yl} -4- pyrrohdin-1 -yl-methyl-benzamide, N-{4-methoxy-7-thiophen-2-yl-ber^oi^ia2nl-2-yl)-4-pyrrolidin-l-yl-methyI-beQzamide, N-[4-metho^-7-(2-p>Tidin-2-yl-thia2«l-4-ylJ-benzothiazol-2-yl]-4-pyrrolidin-l-yl- methyl -benzamide, 4-cWoro--N-(4-methoxy-7-morpholin-4--yl--bciizothiazol--2-)"l)-3-pyrroIidiii-l-yl-inethyl- benzamide, N - (4-methoxy-7-morphoHn^-yl-benzothiaZol-2-yI)-3-pyrrolidin-. 1 -yl-methyl- benzamide, N- C4-methoxy-7-morpholin-4-yl-benzQthiazol-2-yI )-4- (2-roethy!-iinidazol-1 -yi- methyl )- benzamide and N-(4-methoxy-7-morpholin-4-y]-benzothiazol-2-yI)-4"(4-methyl-piperazin-l-yI- methyl)-ben2amide. 8. The compounds of formula IA in accordance with claim 1> wherein R* is an oprionaJly substituted five or six membered aromatic or non aromatic heterocycle. 9. The compounds of formula IA in accordance with claim 8, wherein the five or six membered aromatic or non aromatic heterocycle is morpholine or piperazine. 10. A process for preparing a compound of formulas l-A as claimed in claims 1-9 which process comprises

Full Text

To a solution of 2-chloro-4-methoxy-7-phenjd-benzothiazole (150 mg, 0.54 mmol), in dioxane (5 ml) was added 3-(aminomethyl) -pyridine (176 mg, 1.6 mmol) and mis mixture was stirred at 100 °C for 18 h.. The solvent was then evaporated and the mixture taken up in methanol (8 ml) and ultrasonnicated for 10 min. to precipitate the product, which was washed with methanol (5 ml), and dried under vacuum (0.05 mmHg, 60 °C) to afford the title compound as a white solid (58 mg, 31 % yield), MS: m/e=348.3 (M+rf).
Following ike general method of example 174, the compounds of examples 175 to 184 were prepared
Example 175 f4-Memoxy-7-phenyI-benzotbia741-2-yIVpyrid4-4y1m4hyl-aniine
Using 4-(aminomethyl)-pyridine the title compound was obtained as a pale yellow solid (17 % yield), MS: m/e=343.3 (M+rT).
Example 176 f4-Methoxv-7-phenvl-ben2Pl4azol-2-yl)-pyridin-2-y]rnethy1-arninp
Using 2-(aminomethyl)-pyridine the title compound was obtained as a white solid (32 % yield), MS: m/e=343.3 (M+H*).
Example 177 Ben24-(4-memoxv-7-phenvJ-hf4zothiazol-2-YlVamine
Using benzylamine the tide compound was obtained as a white solid (54 % yield), MS: m/e=347.3 (M+H1").
Example 178 (2-Methoxy-ethvl W4-metiioxv-7-phenvi-benzothiazol-2--vl 1-amin >»
Using 2-memoxy-ethylainrne the title compound was obtained as a white solid (56 % yield), MS: m/e=315.3 (M+H*).
Example 179 Cvdopropv4Tri«!4hyl-l"4-methoYv-7-phenvl-b4"7nt>iia7ii1-2-vl"l-ammp

Using ammomethyl-cydopropane the title compound was obtained as a white solid (68 % yield), MS: m/e=311.2 (M+H+).
Example 180
f4-Methoxy-7-phenyl-benzomiazol-2-yl)-(2-pyrio44 r {12}
Using 3-(2-aminoethyl)-pyridine die crude product was obtained which was converted to its hydrochloride salt with excess 5N HCI/EtOH (2.5 eq.) and then purified by reversed phase preparative HPLC using a C18 ODS-AQ column, with a water (0.1% TFA) /acetonitrile gradient After pooling the product fractions and evaporation of solvents the i title compound was obtained as a white foam (59 % yield), MS: m/e=362.2 (M+H*),
Example 181
N-f4-Memoxv-7-phenyl-penzotriiazol-2-vIV4 TryHrni-hloridg salt (1:2)
Using 2-(dimethylammo)-emyiamine the crude product was obtained which was converted to its hydrochloride salt with excess 5N HCI/EtOH (2.5 eq.) and then purified by reversed phase preparative HPLC, using a C18 ODS-AQ column, with a water (0.1% TFA) /acetonitrile gradient. After pooling the product fractions and evaporation of solvents the title compound was obtained as awhite foam (80 % yield), MS: m/e=3283 (M+H*).
Example 182
■ f4Methoxv4-phen4-beiizothjazQl-4-yl)-44 salt (1:2)
Using 4-{2-aminoethyl)morpholine the crude product was obtained which was converted to its hydrochloride salt with excess 5N HCI/EtOH (2.5 eq.) and then purified by reversed phase preparative HPLC, using a C18 ODS-AQ column, with a water (0.1% TFA) /acetonitrile gradient. After pooling the product fractions and evaporation of solvents the title compound was obtained as a white foam (67 % yield), MS: m/e=370-3 (M+H*).
Example 183
f4-Methoxy-7-phenvI-bgnTfttliiq4l-2-yl)-f2-piperidm--l-vi-ethvlVaminehvdr(v:hTnride salt f 131

Using l-(2-aromoethyl)-prperidine the crude product was obtained which was converted to its hydrochloride salt with excess 5N HG/EtOH (2.5 eq.) and then purified by reversed phase preparative HPLC, using a CI 8 ODS-AQ column, with a water (0.1% TFA) /acetonitrile gradient After pooling the product fractions and evaporation of solvents the title compound was obtained as a white foam (57 % yield), MS: m/e=368.2 (M+H*).
Example 184
2-(4-Memoxv-7-phenvI-benzothiazol-2-yIamino)-ethanol hydrochloride salt f 1:1)
Using ethanolarnine the crude product was obtained which was converted to its hydrochloride salt with excess 5N HCl/EtOH (2.5 eq.) and then purified by reversed phase preparative HPLC, using a C18 ODS-AQ column, with a water (0.1% TFA) /acetonitrile gradient After pooling the product fractions arid evaporation of solvents the title compound was obtained as a white foam (60 % yield), MS: m/e=300.4 (M-s-H*).
Example 185
[4-Memoxy-7-f2-memyl:pyridm-4-vD-benzotM arid methyl ester
The title compound is sysnthesised from (7-iodo-4-methoxy-benzothiazol-2-yl)- Example 186
(4-Menioxy-7-morpbnlin-4-y1-bm7otHazoI-2-vl)-carbamic acid methvl ester
Carbamate formation using the same procedure as for (4-methoxy-benzothiazol-2-yl)-carbamic acid methyl ester yields the product as off-white solid in 58% yield. MS: m/e= 324 (M+H1").
Example 187 f4-Memoxy-7-phenvl-benzothia;4l-2-vl)-cafbamic acid benzyl ester
To a stirred solution of 2-ammo4methoxy-7-phenyl-berizothia2ole (512 nig, 2 mmol) in pyridine at 90 °C was added benzyl chlorofonnate (33 ml, 23.4 mmol) in three portions over 6 hours. The reaction mixture was then evaporated to dryness and partioned between CH2CI2 (50 ml) and saturated aqueous NaQ solution (50 ml), the aqueous phase was separated and extracted further with CH2C12 (2x 50 ml) and the combined organic phases dried, fiTtered and evaporated. The crude residue was then chromatographed over SiG2

(Merck 230-400 mesh) eluting with CHaCl4tOAc (4:1) to afford the title compound as a white foam (620 mg, 79 % yield), MS: m/e=391.2 (M+H*).
Example 188
(4-MemoxY-7-vmyi-beiizotluazoI-2-yl)-carbamic acid methyl ester
a) f 7-Iodo-4-methoxy-benzotbiazol-2-yl)-carhaiTiic acid methyl ester
(4-Memoxy-benzothiazol-2-yl)-carbamic acid methyl ester (31.0 g, 130 mmol) and sodium acetate (32.3 g, 394 mmol) are dissolved in 400 ml of glacial acetic acid and slowly treated with iodine monochloride (13.5 ml, 264 mmol) at 0 °C. The reaction mixture is then slowly warmed to room temperature and stirred for 15 hours. After addition of water (1.31), the formed precipitate is filtered off and washed with water. The filter cake is then dissolved in a minimal amount of tetrahydrofurane (about 150 ml) and decolorized with 1M aqueous sodium thiosulfate. The product is precipitated by the addition of water (about 2.01), filtered off and dried at 60 °C for 12 hours. 42.3 g (89 %) white solid. MS: m/e= 364 (M*).
b) (4-Memoxy-7-vinvI-benzothiazol-2-vl"l-carbamic acid methyl ester
(7-Iodo-4~memoxp-benzothiazol-2-yl)-carbamic acid ester (1 part), vmyltributylstannane (1.0 equivalents) andietrakis-(triphenylphosphme)-paflacHum(0) (0.1 equivalents) are combined in dioxaiie (25 parts) containing 2M Na2C03 (4.0 equivalents) and heated to reflux for 24 hours. The reaction mixture was evaporated, washed with brine and dried over MgSO*. After evaporation to dryness the product was isolated by flash chromatography (silica, eluent ethyl acetate/hexanes) as a white solid (60 %). F.p.: 138-139° C.
Example 189
4-Fluoro-N-f 4-methoxy-7-vinyl-benzothiazol-2-vl) -hepramide
al 4-Memoxy-7-vmvl-benzothiazoi-2-ylamine
(4-Memoxy-7-vmyl-berizolhiazol-2-yl)-carbamic acid methyi ester was dissolved in ethvlenglycol/2N KOH (2:1) and stirred at 100 °C for 3 hrs. Then water was added and the mixture was extracted with CH2Q2, the organic phase was washed with brine and dried over MgSO*. After evaporation the residue was crystallized from CH2CI2. White crystals (64%); F.p.: 155-159 °C.

b) 4-Huoro-N-f4-methosy--7--vinvl-benzothiazol-2-vI")--bpn7.3miHp
Following the general method of example 1 the title compound was obtained from 4-memoxy-7-vmyl-benzothiazol-2-ylamine and 4-fiuoro-benzoic acid chloride as a white solid (85 %); F.p.: 198-199° C
Example 190
f4-Methoxy-7-propenYl-benzothiazol-2-yl")-carbarnic acid methyl ester
Following the general method 188b) the title compound was obtained from (7-iodo-4-methoxy-benzothiazol-2-yl)-carbamic acid methyl ester and tributyl-propenyl-stannane as a yellowish solid (75 %); F.p.: 153-156 °C.
Example 191
N-f7-Ethyl4-methoxy-berizolhia2ol-2-yi1--4-fluoro-benzamide
100 mg of 4-fiuoro-N-(4-methoxy-7-vmyl-benzothiazol--2-yi)-benzamide (0.3 ramol) were dissolved in methanol (100 ml) and Pd/C (4 mg) were added. The reaction mixture was hydrogenated for 2 hrs. After filtering and evaporation of the solvent the crude product was subjected to column chromatography (silica gel, eluent MeQH/CHjCk 1:9). The title compound was obtained in form of white crystals (79 %); F.p.: 165-167° C.
Example 192 (7-Acetvl-4-methoxy7benzpthiazol-2-yl)-carbamic acid methyl ester
According to the method described for example 188b) the title compound was obtained from (7-iodo-4-memoxy-benzothiazol-2-yl)-carbamic acid methyl ester (1 equivalent) and (l-ethoxy-vinyl)-tributylstannane (1 equivalent) as a white solid (34 %); P.p.: 238-240 °C.
Example 193
Rac-f7-(l-Hvdroxv-ethyl)-4"methoxy-benzotbia2ol-2--yl1-carbamir acid methyl ester 0.05 g of (7-acetyl-4-memoxy-benzothiazoI-2-yi)-carbamic acid methyl ester (0.00018 Mol) were dissolved in ethanol (30 ml) and 0.028 g of NaBFL, (0.00072 Mol) were added. After stirring at 40 °C for 24 hrs. the reaction mixture was diluted with water, extracted with CHaCb, the organic phase washed with brine and dried over MgSC>4. After chromatography on silicagel with CHaCk/MeOH 97:3 the title compound was obtained as a white solid (38 %); F.p.: 179 °C (dec).

Example 194 (intermediate)
Rac-f 7-f2-Bromo-I-hydroxy-emvl)4memQxy-ben2othiazol-2-yi1-carbamic add methvi ester
1.5 g of (4-methoxy-7-vinyl-benzomiazol-2-yl)-carbamic add methyl ester (0.0057 Mol),
dissolved in THF (60 ml) were treated with H20 (6 ml) and 1.0 g of NBS (0.006 Mol) at
room temperature for 15 min. Then the solvent was removed, the residue taken up in H2O
(30 ml) and extracted four times with ethyl acetate (50 ml). The combined organic phases
were washed with brine and dried over MgSCV After evaporation the crude product was
subjected to column chromatography (sihcagel, ethyl acetate). The title compound was
obtained as a white solid (78 %)> F.p.: 150-155 °C.
Example 195 (intermediate)
f7-(2-Bromo-l-hvdroxy-propyl)-4-memoxy-ben20tm4ol-2-yll-carbainic add methyl ester
According to the method described for the example above the title compound was obtained from (4-memoxy-7-propenyl-ben2othiazol-2-yl)-carbamic add methyl ester as a foam and carried on to the next step without further purification and characterization.
Example 196 (intermediate)
(7-Bromoacetyl4-memoxy-benzotHa2ol-2 1.6 g of rac-[7-(2-bromo-l-hydroxy-emyl)-4-meliioxy-benzothiazol-2-yl]-carbamic acid
methyl ester (0.0044 Mol) were dissolved in CHCU (100 ml) and treated with 3.8 g of
MnOj (0.044 Mol) for 3 hxs. at 70 °C. The hot reaction mixture was filtered and
subsequently concentrated. The crude product was crystallized from Et20 to yield the title
compound as a beige solid (73 %); F.p.: 250-260 °C (dec).
Example 197 (intermediate)
[7-(2-Bromo-propionyl)-4-methoxy-bsnzotbia7ol-2-yH-carbainic add methyl ester
5.0 g of [7-(2-bromo-l-hydrc«y-propyl)-4-memoxy-benzothiazol-2-yl]-carbamic add methvi ester 0.0133 Mol) were suspended in water (30 ml) and 2.0 g of Cr03 (0.02 Mol), dissob/ed in acetic add (30 ml), were added. The reaction mixture was heated to 70 °C for 2 hrs. and then evaporated to dryness. The residue was taken up in sat NaHC03 (200 ml),

extracted 4x with ethyl acetate (200 ml each) and the combined organic phases were dried over MgS04. The title compound was obtained as orange crystals (74 %); P.p.: 199-201 °C
Example 198
(4-Methoxy-7-thiophen-2-yI-benzothiazol-2-vI"l-cariiaTm"r acid methyl ester
Following the method described for (4-methoxy-7-vmyl-benzothiazol-2-yl)-carbamic acid methyl ester (Example 188b) the title compound was obtained from (7-iodo-4-methoxy-benzothiazol-2-yI)-carbamic acid methyl ester and 2-tributylstannyl-thiophen as a yellowish solid (41 %); 160-165 °C
Example 199
[4-Methoxy-7-(5-memyl-thiophen-2-Yl)-benzo1hiazol-2--yll-carharnir. acid methyl ester
Following the method described for (4-memoxy-7-vmyI-benzothiazol-2-yO-carbarnic acid methyl ester (Example 188b) the title compound was obtained from (7-iodo-4-methoxy-benzothia2ol-2-yl)-carbarnic acid methyl ester and 2-tributylstannyl-5-methylthiophen as a yellowish solid (40 %); 267-274 °C (dec).
Example 200
r4-Methoxy-7-(2-memyl-miazol-4-Yl)-ben2othiazol-2-yl")-caTbarnic acid methyl ester
1.3 g of (7-bromoacetyl-4-memoxy-benzothiazol-2-yl)--carbamic acid methyl ester (0.0036 Mol) and 0.27 g of thioacetamide (0.0036 Mol) were dissolved in dioxane (30 ml) and stirred for 4 hrs. at 70 °C. After evaporation of half of the solvent water (40 ml) was added and the pH adjust to 7 with sat. NaHC03. A solid precipitated, which was isolated and then subjected to column chromatography on silicagel using ethyl acetate as eluent. The title product was isolated as an off-white solid (27 %); P.p.: 186-188 °C.
Example 201
{4-Memoxy-7-f2-f6-memyl-p™dm-3-v4-thia7ni-4-yl|-be methyl ester
According to the method described above the title compound was obtained from (7-bromoacetyI-4-memoxy-ben20thiazol-2-yI)-carbamic acid methyl ester and 2-meliiylpyridine-5-thiocaboxamide as a yellowish solid (73 %); F.p.: 240-242 °C.

Example 202
[4-Metfaosy-7-f2-pyriHiTi-?.-4-tfaiazol44Vbenzothia2ol-2-vl1-carbamic acid methvi ester
According to the method described above the title compound was obtained from (7-bromoacet44methoxy-benzotbiazol-2-yl)-carbaniic acid methyl ester and pyridine-2-thiocaboxamide as a dark red solid (63 %); F.p.: 207 °C.
Example 203
{7-[2-(tert-ButoxvcarbonYlammo-methyiVtHa carbamic acid methyl ester
According to the method described above the tide compound was obtained from (7-bromoacetyi-4-memoxy-benzothiazol-2-yi)-carbarnic acid methyl ester and thiocarbamoylmethyl-carbaniic acid tert-butyl ester as a white solid (26 %); MS (ISP): m/e = 451 (M+rT).
Example 204
f7-f2-Aroinomethvl-thiazol4vi)-4-methoxy-benzotfaiazol-2-vl1-carhamiradd ester hydrochloride f 1:11
0.075 g of {7-l2-(tert-butoxycarbonylainmo-memyl)-lhiazol-4-yl]-4-methosy-benzothiazol-2-yl}-cajbarnic add methyl ester (0.00017 Mol) were stirred in 2 ml of 2.5 M HCl/MeOH for 4 hrs. Upon cooling to room temperature a predpitate formed, which was filtered off, washed with hexane and dried. The title compound was obtained as a white solid (70 96), F.p.: 220-230 °G
Example 205
r7-(2-Dirnetriylaminomrfhvl-tmazol-4-yl)4m
methyl ester
According to the method described for l4-methoxy-7-(2-methyl-thiazol-4~yl)-benzothiazol-2-yl]-carbamic add methyl ester the title compound was obtained from (7-bromoacetyl-4-niedioxy-benzotHa2ol-2-yl)-carbamic add methyl ester and dimethylajnino-thioacetamide as an off-white solid (11 %); F.p.: 185-189 °C (dec).
Example 206
\ 7-f23-DimethyI-thiar4I-4"Vl1-4-pri4Hoxv-benzothiazol-2-ylI-carbaniLc add methyi ester

According to the method described above the title compound was obtained from [7-(2-bromo-propiony!)-4-methosy-benzotbiazol-2->d]-carbamic acid methyi ester and thioacetaraide as an off-white solid (42 %); F.p.: 180-181 °C (dec).
Example 207
f4-MemoxV-7-[2-flritv1-3TriinoVtiiiazoI-4-yll-ben?othiazol-2-,yli-carharnit: acid methyl ester
According to the method described above the title compound was obtained from [7-(2-bromo-acety!)-4-methoxy-benzothiazol-2--yi] -carbamic acid metihyl ester and trityl-tbiourea as an off-white solid (53 %); F.p.: 135-140 °C.
Example 208
[7-(2-Ami44tbia7ol4yl)4-methoxy-hen7.nthia7nl-2-y1|-r4rbaTriic acid methyl ester
0.070 g of {4-memoxy-7-[2-(trityl-ammo)-tbia7x>l-4 add
methyl ester (0.00012 Mol) were heated to reflux in 2 ml of 2.5 M HCl/MeOH for 4 hrs. After cooling to room temperature the pH was adjusted to 7 upon drop wise addition of sat. NaHCC>3. A predpitate formed, which was filtered off, washed with ethyl acetate and dried. The title compound was obtained as a white solid (23 %), F.p.: 293-296 °C (dec.).
Example 209
[7-(2-T4TTi4hy1amino-tiuazol4yI)-4-methoxy-bep7-nthia741-2-vll-carbaniif: acid methvl ester
According to the method described above the title compound was obtained from [7-(2-bromo-acetyl)-4-methoxy-benzothiazol-2-yl]-carbamic acid methyl ester, NN-dimethyl-thiourea and triethyiamin as an off-white solid (86 %); F.p.: 185-195 °C.
Example 210
[4-Memoxy-7-f2-pyrrolidin-l-yl-thiazol-4-yl)-ben7xtthia2ol-2-yll-carbamic add methyl ester
According to the method described for the example described above tie title compound was obtained from [7-(2-bromo-acetyl)-4-metnoxy-benzothiazol-2-yl]-carbarnic add methyl ester and 1-pynoUdine-carbothioamide as an off-white solid (16 %); F.p.: 199 °C.

Example 211
[4-Methoyy~7-f2-piperidiqrl-yl-tfaiazol4yl)-beri2othiazol-2-vl1-carbamic acid methyl ester
According to the method described above the title compound was obtained from [7-(2-bromo-acetyi)-4-methoxy-ben2othiazoI-2-yl] -carbamic acid methyl ester and 1-piperidine-carbothioamide as an off-white solid (71 %); F-p.: 209 211 °C.
Example 212
[4-Methoxy-7-(2-morphoh4-4-yl-tbjazol4Yl)-benM acid methyl
ester
According to the method described above die title compound was obtained from [7-(2-bromo-acetyi)-4-methoxy-benzothiazol-2-yi]-carbamic acid methyl ester and 1-morphohne-carbotbioamide as a yellowish solid (41 %); MS (ISP): m/e = 407 (M+H*).
Example 213
J4-Memoxy-7-f2-(4-memyl-pipera2mTl-yl)-thiazol4 acid methyl ester
According to the method described above the title compound was obtained from [7-(2-bromo-acetyl) 4methoxy-benzotmazol-2-yi] -carbamic acid methyl ester and 4-methyi-l -piperazmethiocarboxamide as a brownwish solid (41 %); F.p.: 143 °C
Example 214
[7- (2-tert-Butoxycarbonylarnino-1 H-irni64zol-4-yl)-4-meihoxy-berizothiazoi-2-vll -carbamic acid methyl ester
0.25 g of (7-bromoacetyl-4-memoxy-benzothiazol-2-yi)--carbamic acid methyl ester (0-0007 Mol) and 0.33 g of tert-butoxycarbonylguanidine (0.0021 Mol) were heated to reflux in acetonitril (3 ml) for 3 hrs. After evaporation of the solvent the residue was triturated with water (10 ml) and filtered. The filtrate was evaporated and the residue subjected to column chromatography (siUcagel, ethyl-acetate/hexanes 1:1) to yield the title compound as a white solid (17 %); F.pj 255-265 °C.

Example 215
r7-f2-Airnino-lH-iiiudazol-4-yl)4methoxy-benzodMazol-2-Yl]-carhaniic acid methyl ester
0.04 g of [7-(2-tert-butoxycarbonylairimo-lH-imidazol-4-yO
yl]-carbamic acid methyl ester (0.0001 Mol) were heated to 60 °C in HO/MeOH (2.5 M, 2 ml). After evaporation of the solvent the residue was dissolved in water (5 ml) and the pH was adjusted to 8 with sat NaHCOj. The water was evaporated and the residue triturated in ethyl acetate where a precipitation formed. This was isolated and dried to yield the title compound as a grey solid (16 %); F.p.: 225-235 °C.
The following examples were prepared according to the general method described for 4-methoxy-7-vmyI-benzolhiazol-2-yl-amine (Example 189a) from the corresponding carbamic acid methyl ester.
4-Memoyy-7-("2-morpTi9lin-4-vl-thiazol-4-vlVbeiizotruazol-2-yi-araine
Obtained as a white solid (73 %); F.p.: 289-292 °C. 4-Mefao:re-7-[2-(4-me&vl-piperarin-1-vl)-thiazol4
Obtained as a light yellow solid (81 %); F.p.: 176 °C (dec).
4-Methoxy-7- \2- (6-memyl-pyridin-3-vl)-thiazol-4-yl1 -bpn7Qthiazol~2-yl-amine
Obtained as an off-white solid (94 %); MS (ISP): m/e - 355 (M+FF). 7-f7--Airiino-ihiazol-4-vl)-4-memoxy-benzothia2ol-2-yl-amine
Obtained as a white solid (56 %); MS (ISP): m/e = 279 (M+FT).
7-f2-Dimemylarnino-thiazol-4-yl)-4-memoxy-ben2othia2ol-2-yi-arnm
Obtained as a beige solid (62 %); F.p.: 225-238 °C.
4-Methoyy-7-miophen-2-4-benzothiazol-2-y]-aimne
Obtained as a light brown solid (85 %); F.p.: 215-219 °C.
4-Metfaory-7-f2-pyridm-2-vi-ftta7rii-4-yl)-berizomiagol-2-vi-aniine
Obtained as a light yettow soEd (67%); F.p.: 302 "C (dec).

4-Metfaox7-7-f2-pyiToHdin-1-y4-iiiia2ol4yiVben2otlna7.n1-?.-v1-arnirifi
Obtained as a light brown solid (99 %); P.p.: 270 °C (dec).
4-Metfaoyy-7-f2-piperidin-1-4-thiazol4ylVbenzofliiay.nl-9.-Yi-amiTip
Obtained as a light brown solid (75 %); MS (ISP): m/e = 347 (M+PT).
4-Methox>r-7-f2i-metfa4-thi37n]4yi)-benzothia4ol-2-Td-4mine
Obtained as an off-white solid (81 %); P.p.: 262-265 °C.
4-Methoxy-7r (5-roethvi-thinphen-2-yl)-benzothia7-oI-?-yl -aminp
Obtained as an off-white solid (81 %); F.p.: 195-205 °C (dec).
7-(2,5-PiT"4>"y4-th4a7i41U-444-melhoxv-berlzo1hiazol-2-1|d-amine
Obtained as a yellow solid (5 %); P.p.: 201-20 3 °C.
FoUowing the general method of example 1 the fallowing examples were obtained from corresponding benzothiazol-2-yl-amines and 4-fluoro-benzoic add chloride:
Example 216
4-Huoro-N-U-methoxy-7-f2-morpholm-4-vl-lbJazoI-44vlVbenzothia2ol-2-vl1-benzaTTiidg Obtained as an off-white solid (53 %); P.p.: 225-227 °C.
Example 217
N-r7-f2-Ammo-tiuazol-44y1)-4-me&oxy-ben Obtained as a white solid (85 %); F.p.: 262-264 °C.
Example 218
4-F]uoro-N-f4-melho3re-Xf9-f6-meth)fl-pp4T4 benzamide
Obtained as an off-white solid (79 %); MS (ISP): m/e = 477 (M+fT).

example zi?
N-{7-(2-Dim4iiYlamipo-thiazol-4-Yl)-4-metbj:iC4 Obtained as a light yellow solid (29 %); P.p.: 218-220 °C
Example 220 4-Fluoro-N-f4-metboxy-7-tMophem-2-yl-benzotfaia2oI--2-ylVbenzainide Obtained as a light yellow solid (72 %}; P.p.: 242-250°C.
Example 221
4-Fluoro-N-l4-methoxy-7- \2-( 4-methyI-piperazin- l-yl)-thiazol-4-yl| -benzothiazoI-2-yll-
benzamide
Obtained as an off-white solid (66 %); F.p.: 138 "C (dec).
Example 222 4-Huoro-N-r4-metb.oxy4-7-(2-pyridin-2-4-diiazol-4-ylVben2otlu4tzol-2-yl1-benz3TTiiH4
Obtained as an off-white solid (92 %); F.p.: 150 °C (dec).
Example 223 4-Fluoro-N- r4-methoxy-7-(2-pyrrolidin- l-yl-thia2ol-4-yl)-benzothiazol-2-yI1 -Ivnra mid* Obtained as an off-white solid (82 %); MS (ISP): m/e = 455 (M+H*).
Example 224 4-Fluoro-N- f 4-methoxy-7-f 2-methyl-tbiazol-4-yl)-benzothiazol--2-"id1 -benzamide Obtained as a white solid (36 %); F.p.: 217-219 °C.
Example 225 4-Wnoro-N-f4-methoxv-7-("5-melhyI-thiophen-2-4)-hf4n74thiazol--2-yll--benzamide Obtained as an off-white solid (70 %); P.p.: 192-196 °C (dec).

Example 226
N-f7-(2,5-Dimethyl-lfaiazol-4-yl)-4-memory-Hgn4 Obtained as an off-white solid (42 %); F.p.: 205-206 °C (dec.).
Example 227
4-ChloromethvI-N44-methoxy-7-f2-morpholin-44 benzamide
0.165 g of 4-methoxy-7-(2-morpholm-4-yi-thiazd4-yl)-benzothiazol-2-)4aniine (0.00047 Mol) were dissolved in dioxane (5 ml) and combined with. 0.1 nil of triethyiamine (0.0007 Mol), 0.006 g DMAP (0.000047 Mol) afcd a solution of 0.116 g of 4-(chlormethyl)benzoylcblorid (0.00062 Mol) in dioxane (1 ml). The reaction mixture was stirred for 6 hrs. at 70° C. After cooling down to room temperature, water (10 ml) and sat. NaHCC>3 (10 ml) were added. A precipitation formed. It was filtered, washed with water and tried. This crude product was subjected to column chromatography (sOicagel, CH2Cl2/MeOH 19:1). The tide compound was obtained as a light yellow solid (65 %); F.p.: 166-168 °C.
The following examples were prepared from the corresponding 7- substituted 4-meihoxy~ ber4thiazol-2-yl-amirie$ according to the above described method:
Example 228
4-Chloromethyi-K- J4-methoxy-7-f 2-f 6-methvl-pyricUn-3-ylVtbJazol-4-iAl -benzotbiazol-2-yi}-ben7.amide
Obtained as an off-white solid (68 %); F.p.: 230-250 °C.
Example 229
4-Cbloromethvl-N-{4-methoxy-7- [2- (trit4-ammo)-tbia2ol4yll-beiizothiazol-2-Yl\-benzamide
Obtained as a white solid (42 %); F.p.: 163 °C (dec.).
Example 230
44Chloromethvl-N-r7-f2-Himrthylamin4-t4 bemsBHu?

Obtained as a light yellow solid (36 %); F.p.: 183-186 °C.
Example 231 4-CMorome&yl-N-f4-me&oxy-7-lHophen-2-4-bei4othiazol-2-ylVbenzaroide Obtained as a light yellow solid (60 %); F.p.: 183-209 °C (dec).
Example 232
4-Chloromethyl-N-f4-methoxy-7-(?.-pvridin-2-yl-thia4 henTamide
Obtained as a light brown solid (79 %); F.p.: 195-201 °C.
Example 233 4-Chloromethyl-N- f 4-methoxy- 7- f 2-methyl-thiazol-4-yl"l-berizothiazol-2-yl1 -benzamide Obtained as a white solid (72 %); F.p.: 140-145 °C.
Example 234
4-ClrioromethYl-N-f4-roethoxy-7-f5-methvl-i4 benzamide
Obtained as a yellow solid (93 %); F.p.: 130-146 °C.
Example 235
4-U(2-Methoxv-ethylVmelhyl-aminn]-methyl4N-f4-memoxy-7-(2-morpholni-4-yi-th iazol-4-yl Vbenzothia2ol-2-y11 -b*»r>Tami H e.
0.035 g N-(2-methoxyethyl)-methylamine (0.00039 Mol) and 0.064 g (4-chloromemyl-N-
[4-methoxy-7-(2-moipholm-44yl-tMazol4y4
Mol) dissolved in THF (2 ml) were heated to reflux for 4 hrs. After cooling to room
temperature and evaporation of the solvent the residue was triturated with water (7 ml). A
precipitation formed, which was filtered, washed with water and dried yielding the title
product as an off-white solid (79 %); F.p.: 100-110 "C.
The following examples were prepared according to the method above from N-(2-methoxy-benzothiazol-2-yl] -benzamides:

Example 236
4-Jf(2-MethoYy-em7l)-memyI-ammoUmethvl}-N-f4-m thiazol-4-yll -benzothia2ol-2-yn-benzamide
Obtained as a white solid (79 %); F.p.: 119-128 °C
Example 237
N-[7-f?.-Aminn-itoazol4yl)4methoxv-benzothiazol-2-414-fff2-memoxy-ethyD-methyl-aminol -methyl] -benzamide
0.1 g of 4-{[(2-melhox7-e&yl)-methyl-arnmo]-methyl}-N-{4-memoxy-7-[2-(trit7l-ammo)-tinazol-4-yl]-benzothiazol-2-yi}-benzainide (0.00014 Mol) were treated with cc HC1 (0.03 ml) in MeOH (1 ml) for 1 h at reflux. After evaporation of the solvent the residue was taken up in water (10 ml), treated with sat NaHCOs (10 ml) and extracted 4x with ethyl acetate. The combined organic phases were dried over Na2SO Example 238
44ff2-Memo:re-emyiymemvl-aTTiinf»1-m44 vO-thiazol-4-Yn -benzothiarol-2-yIl-benzamide
Obtained as a light yellow foam (69 %); MS (ISP): m/e = 560 (M+FT).
Example 239
N47-f2-Dimethvlainmo-tbiazol4yl)-4-memox4 ethvD-methvi-aminol -methvU-benzamide
Obtained as a light yellow solid (47 %); F.p.: 85-95 °C.
Example 240
4-lk2-Metfaoxy-elhyI)-memvI-annno1-methyll-N-(4-methoxy-7-thiophen-2-vl-i benTnfhiazoI-2-yn-benzamide

Obtained as a light beige solid (44 %); F.p.: 58-78 °C.
Example 241
4-W2-Memortr-ethvi)-methvi-ammolmediTi4N-f4-m 4-yi )-benzothia2ol-2-yfl -benzamide
Obtained as a light yellow solid (54 %); MS (ISP): m/e = 546 (M+rT).
Example 242
4-nf2-Methoxy-ethviVmethvl-animo1-methvll-4 benzothia2ol-2-yil -benzamide
Obtained as a white solid (36 %); F.p.: 140-145 °C.
Example 243
4-4f2-Methoxv-eth4Vmeth4-aminn]-melh4}-N-f4-methomr-7-f5-meth4thiophen-2-yi) -benzothiazol-2-vn -benzamide
Obtained as alight beige solid (73 %); F.p.: 83-90 °C.
Example 244
N- f 4-Methoxy-7-f2-morpholin-4-yi-thi4nI-4-4)-benzotmazo?-2-Yl]-4-pTTrolidin- 1-vi-methyl-benzamide
0.032 g pyrrolidine (0.00045 Mol) and 0.075 g (4-chloromethyl-N-[4-methQ35y-7-(2-mo4holm-4-yl-1hia2ol-4-yl)-beiizoiiiiazol-2--yl]--benzamide (0.00015 Mol) dissolved in THF (2 ml) were heated to reflux for 1 h. After cooling to room temperature and evaporation of the solvent the residue was triturated with water (7 ml). A precipitation 1 formed, which was filtered, washed with water and dried yielding the title product as an off-white solid (87 %); F.p.: 120-130 °C
The following examples were prepared aeeoording to the method above from pyrrolidine and the corresponding 7- substituted 4-&bromelhyl-N-[4-melhoxy-ben20lhiazol-2-yl]-benzamides:

Example 245
N-i4-Memoxv-7- f 2-f 6-methvl-pvridin-3-vi Vthiazol-4-vl 1 -benzothiazol-2-vll-4-pvreoh"dm- 1-yi-methyl-benzamide
Obtained as a light brown solid (58 %); F.p..- 230-231 °C.
Example 246
N-l4-Methoxy-7-f2-flrifrri-ainmo)-thiazol-4-yl1-be methvl-benzamide
Obtained as a light yellow solid (89 %); P.p.: 122-135 "C.
Example 247
N- [7-f 2-A4inrwtKiqzol-4-4)-4-metlioxy-beii20tHazol-2-vl1-4-pyrrolidJn- 1-yi-methyl-hpnTamidebydrni-bloride (1:1)
0.055 g of N-{4-methoxy-7-[2-{tiit)d-ainmo)-tbiazol-4-vl]-benzotiiiazol-2-yi}-4-pyrrolidin-l-ylmetlt)i-benzamide (0.000078 Mol) were dissolved in MeOH (0.5 ml) and ccHQ (0.015 ml). After refluxmg for 1 h the solvent was evaporated, the residue treated with ethyl acetate, filtered and isolated This material was triturated in EtOH whereby crystals formed, which were washed with EtjO. After drying the title compound was obtained as a white solid (62 %); F.p.: 228-240 °C.
Example 248
N-i7-f2-DJTnetHy1aTninn-tHa7X>l-4-YD-4-metfao4 methyl-benzamide
Obtained as a light yellow solid (75 %); P.p.: 120-136 °C.
Example 249
N-(4-Methoxv-7-thiophen-2-yl -ben7Jrthia7ol-2-yl4-4-pvrrolidin-l -vi-methyl-hemaTniHf; Obtained as a light beige solid (47 %); P.p.: 174-190 °C (dec).

Example 250
N44-Methoxy"7-(2-pyridm-2-vi-tfo"azoI-4-yi)-ben2a44 methvi-benzamide
Obtained as a light fellow foam (48 %); MS (ISP): m/e = 528 (M+H*).
Example 251
N- f 4-Methoxv-7-f 5-methvI-thiophen-24)-beii2omiazol-2-yl1 -4-rmroh4-l-yl-rnethyl-
Obtained as a light beige solid (67 %); F.p.: 140-149 °C (dec).
Example 252
N-f4-Melhoxv-7-(2-rneth4-tMazol4yl)-benzothiazol-2-vi1-4-pyrroHdm-l-vl-me henTamiHp
Obtained as a light yellow solid (44 %); F.p.: 123-134 °C.
Example 253
N-f4-Methoxy-7-tbinpbw-?-yi-benzotbia2ol-2-4)-2-meliiyi-isonicotirjamide
0.21 g of 4-methoxy-7-thiopben-2-yl-beim)tbiazol-2-yl-amine (0.0008 Mol) together with 0.27 ml triethylamine (0.002 Mol), 0.01 g of DMAP and 0.20 g isonicotinic acid chloride (0.001 Mol) were heated to reflux for 20 hrs. in dioxane (10 ml). After cooling to room temperature water (20 ml) and sat. NaHC03 (15 ml) were added. A precipitation formed, which was filtered, washed with water and dried. This crude product was subjected to column chromatography (suicagel, ethyl acetate) to yield the title compound as a yellow solid (58 %); P.p.: 203-211 °C (dec.).
The following examples were prepared accoording to the method above from isonicotinic acid chloride and the corresponding 7- substituted 4-melhoxy-berizothiazol~2-yI-amines:
Example 254
N- f 4-Methoxy-7-f 2-pvriHiTi-7.-4-ihia2ol-4-4Vbenzothiazol-2-yl1 -2-methyl-
isonicotinamide
Obtained as a light yellow solid (38 %); MS (ISP): m/e = 460 (M+H1").

Example 255
N-[4-Memoxy-7-f2-pyrToHdm-l-yl-thia2ol-4-4)-benzotluazol-2-Tdl--2-methyl-isonicotinamide
Obtained as a yellow solid (9 %); P.p.: 195-215 °C.
Example 256
N-(4-Memoxy-7-(2-f4-memvl-pipera2in-l-yl)-thiazo4 isonicotinamide
Obtained as a yellow foam (4 %); MS (ISP): m/e = 481 (M+rT).
Example 257
N- [4-Methoxy-7-f 5-Tnpthyl -thinphen-? -yiVbenzotbiazol-2-vll -2-methyi--isonicotiTiamidf" Obtained as a light orange foam (65 %); MS (ISP): m/e = 396 (M+H*).
Example 258
Morpholine-4-carboxyiic acid (4-methoxy-7- f2-(6-memvl-pyriHin-3-yIVthiazol-4-Yi1-benzothiazol-2-ylt -amide
0.1 g of 4-methoxy-7-[2-(6-methyl-pyridm-3-ylVthia74
(0.00028 Mol) were dissolved in dioxane (2 ml) and treated with 0.047 ml triethylamine (0.00034 Mol) and 0.164 ml of phosgene (20 % in toluene) (0.00031 Mol). After stirring for 2 his. at room temperature 0.122 ml of morpholine (0.0014 Mol) were added and the whole mixture was stirred for 16 hrs. at ambient temperature. Upon addition of water (5 ml) a precipitation formed, which was filtered, washed with water and dried. This crude material was triturated with hot MeOH and after cooling to room temperature filtered. The filtrate was evaporated and the residue subjected to column chromatography (silicagel, CH2Cl2/MeOH + 1 % NH4OH). The title compound was obtained as a light yellow solid (7 %); MS (ISP): m/e = 468 (M+H+).
Example 259
Morpholine-4--carboxyiic acid [4-memoxy-7-f2-py"4iTi-2-vl--tbia7fi14-y]")-benzot>iia7.n1-9-yil -amide
0.1 gof4-metioxy-7-[2-pyricfo-2-yl}-thiazoI444 (0.00029
Mol) were dissolved in THF (5 ml) and treated with 0.063 ml ethyldiisopropylamine (0.00037 Mol), DMAP (1 mg) and 0.029 mg ©f tripbMgese (00)001 Mol). After faeatnofto

reflux for 30 min., 0.0322 ml of morpholine (0.00037 Mol) and another 0.062 ml of ethyldiisopropyiamine were added and the whole mixture was stirred for 16 irxs. at reflux. After cooling to room temperature water (10 ml) was added and the reaction mixture was extracted with ethyl acetate (4x, 15 ml each). The combined organic phases were dried over Na2S04, filtered and evaporated. The residue was subjected to column chromatography (silicagel, ethyl acetate). The title compound was obtained as a light yellow solid (7 %); F.p.: 152-178° C (dec.).
Example 260
Morpholine-4-carboxyiic acid [4-methoxy-7-(2-memvl-1iiiazol-4-Yl)-benzothiazol-2-yll-amide
0,07 g of 7-(2-Ammo-thiazol4yl)4memoxy-beri20thia2ol-2-yl-amine (0.00025 Mol) were suspended in dioxane (4 ml) and treated with 0.028 g of NaH (60 % dispersion in oil) (0.0006 Mol) for 1 h at room temperature. Then 0.11 ml of triemylamine (0.00076 Mol) and 0.07 ml of morpholine-4-carbonylchloride (0.0006 Mol) were added and the reaction mixture was stirred at room temperature for 3 hrs. Then water (15 ml) was added and the reaction mixture was extracted with ethyl acetate (4x, 20 ml each). The combined organic phases were dried over Na2SOfc filtered and evaporated. The residue was subjected to column chromatography (silicagel, ethyl acetate). The title compound was obtained as a light yellow solid (61 %); P.p.: 223-226 °C (dec).
The following examples were prepared according to the method above from morphoIin-4-carbonylchloride and the corresponding 7- substituted 4-rnethoxy-benzothiazol-2-ylamines:
Example 261
Morpholinp-A-carboxvlic acid {4-methoxy-7-f2-f4-methyl-piperariTi-l-yT)-thia7:ol-4-vn-
benzotbia7.n]-2-vU-aTnide
Obtained as a beige solid (40 %); F.p.: 150-170 °C.
Example 262
Morphol"4-4-4Tfeoxylic acid r4-methoxy-7-f?-pippridin-1 -y1-thia7o1-4-y1)-benzothiazol-2-vil-amide
Obtained as a light yellow solid (25 %); P.p.: 227-234 °C.

Example 263
Morpholine-4rcarboxviic acid (4-methoxv-7-tfaiopheD-2-4-bCTT7nt4ia741-?-y?)-aTniHp Obtained as a light beige solid (37 %); F.p.: 175-182 °C (dec).
Example 264
MorphoIine-4-carboxylic acid r4-metfaoxv-7-f5-metfavl-tbiophen--2--TiVben2X)thiazol-2-
yj] -amide
Obtained as a light beige solid (59 %); F.p.: 173-180 °C (dec).
Example 265
4-Hydroxy-piperidme-l-carboxvhc acid r4-methoxv-7-(2-methvi-thiazol-4-vD-benzothia2ol-2-yH -ami dp
To a suspension of 0.070 g of 4-memoxy-7-(2-memyl-tbiazol-4~yl)-benzotm"azol-2--ylamine (0.00025 Mol) in THF (4 ml) at room temperature were added 0.054 ml N-ethyl-diisopropylamine (0.00031 Mol) and 0.001 g DMAP. 0.025 g of txiphosgen (0.000085 Mol) were added and the whole mixture was heated to 70 °C for 1 hr. Then another 0.054 ml N-ethyl-diisopropylaimne (0.00031 Mol) and 0.031 g of 4-hydroxy-piperidin (0.00031 Mol) were added and the reaction mixture was stirred at 70 °C for 1.5 hrs. Upon cooling to room temperature a precipitation formed, which was filtered and washed with THF. The filtrate was evaporated and the residue was subjected to column chromatography (silicagel, CH2Gb/MeOH 9:1). The title product was obtained as a white solid (11 %); F.p.: 145-150 °C.
The following example was prepared according to the above described methode from 4-methoxy-7-(5-methyl-tMophene-2-yl)-benzothiazol-2-yl"amine:
Example 266
4-Hvdroxy-piperidine-l-carboxyHc acid f4-memoxy-7-(5-methvi-tbiophen-2-vD-benzothia7.n"-2-yn -amide
Obtained as a yellow solid (10 %); F.p.: 197-204 °C (dec).
The fallowing example was prepared according to the methode described above from N~metnyl-piperazine and 4-metkoxy-7-(2-methyl-thiazol4yl)-benzothiazal-2-ylamine:

Example 267
4-Methyi-piperazine-l-carboxviic acid f 4-methoxy-7-f2-methyl-thiazol-4-Tiy benzothiazol-2-yn -amide
Obtained as a white solid (8 %); F.p.: 179-181 °C.
Example 268
{2-f4-(44-Me&oxy-7-morphoIin4-yi-benzodn4zoi-2-yIcarbamoyi)-plieDyi?-ediyif-metnyi-carbamic acid tert-butvl ester
Using [2-(4-chlorocarbonyl-phenyl)-ethyl]-inemyl-carbamic add tert-butyl ester the title compound was prepared using the general method of example I as white solid (16 %), MS: m/e= 527 (M+rT).
Example 269
N-f4-Memoxy-7-morpholin-4-yl-beiizothiazol-2-ylV4-flJ44-tetrafluoro-emoxy)-
bpn7amide
Using 4-(l,l,24-tetrafluoro-ethoxy)-benzoyl chloride the title compound was prepared
using the general method of example 1 as light yellow solid (35%), MS: m/e= 486 (M+H*).
Example 270
4-ff2-Mefooxy-ethyl)-methyl-snlfamovl1-N4
2-ylVben2amide
Using (2-methoxy-ethyl)-methyl-sulfamic acid chloride the title compound was prepared
using the general method of example 1 as red solid (44%), MS: m/e= 521 (M+H*).
Example 271
N-f4-Me&oxy-7-mQTpholin-4-vl-beireotbiazol-2-ffi
Using 4-(trifiuoromethyl)-benzoyl chloride the title compound was prepared using the
general method of example 1 as white solid (58 %), MS: mJe= 438 (M+H*).
Example 272 N-f4-Me&oxy47-moiTJho1m-4r-Td-benzotlu42ol-4

Using 3-(trifluoro-methosy)-benzo)d chloride the title compound was prepared using the general method of example 1 as light yellow solid (84%), MS: m/e= 454 (M+H*).
Example 273
N-f4-Methoxy-7-morpholm4yl-benzotMazol-2-yl)4trifluoromemoxv-benraTtiiHft Using 4-(trifluoro-methoxy)-benzoyI chloride the title compound was prepared using the general method of example 1 as yellow solid (77 %), MS: m/e= 453 (M*).
Example 274
4-Em4-N-f4-memoxy-7-morpholm-4-4-benzotlnazol-2-4Vbenzainide
Using 4-ethyi-benzoyl chloride the title compound was prepared using the general method
of example 1 as white solid (21 %), MS: m/e= 397 (M+H*).
Example 275
4-Fluoro-N-(4-methoxy-7-moipholm4-vl-benzotrda2ol-2-vlVbenzamide
Using 4-fluoro-benzoyl chloride the title compound was prepared using the general
method of example 1 as white solid (64 %), MS: m/e= 388 (M+H*).
Example 276
N-(,4-Methoxy-7-morpholm4yl-beiizotHa4ol-2-ylV2-memTi-isonicotmamide
Using 2-methyl-isonicotmyl chloride the title compound was prepared using the general
method of example 1 as white solid (72 %), MS: m/e= 385 (M+H*).
Example 277
N-(4-Methoxy-7-moi4holm44-benzothiazol-2-yl)-beMamide
Using benzoyl chloride the title compound was prepared using the general method of
example 1 as white solid (85 %), MS: m/e= 370 (M+H1").
The following compounds are described according to the general procedure C in Example 126:
Example 278
4-Chloro-3-f f ethyi-f2-metfaory-4hy? }-amJTio J -methyl ?-N-f4-mefaoxf~7-moTphn)m-4-vl~

Using 4-chloro-3-cMoromethyl-benzoyl chloride and emyl-(2-memoxy-emyl)-arnuie the title compoimd was prepared using the general procedure C as off-white solid (69 %), MS: m/e= 519 (M+H*).
Example 279
N-f4-Metho:4-7-morpholm4yl-hm7nthTa7dl-24
Using 3-diloromethyI-benzoyl chloride and memyiUmine the title compound was
prepared using the general procedure C as white solid (44 %), MS: m/e= 413 (M+H*).
Example 280 4-CMoro-N-(4-memoxy-7-moi4holTn4-Yl-ben2othiazol-2-yi)-3-metDYlamin nm4-hyl -
hpn Tan-ride
Using 4-chloro-3-chloromethyi-benzoyi chloride and methylainine the tide compound was prepared using the general procedure C as light yellow solid (69 %), MS: m/e= 447 (M+H*).
Example 281
4-CrJoro-3-{ff2-methoxv-emTlVmemvl-anTinol-mem4}-N-f4-memoxy-7-morpholin-4-
yi-benzothiazol-2-1dVbenzamide
Using 4-chloro-3-chloromethyl-benzoyl chloride and (2-methoxy-ethyl)-methyI-amine
lie title compound was prepared using die general procedure C as off-white solid (54 %),
MS: m/e= 505 (M+H1").
Example 282
4-Chloro-3-f(2-memoxv-emvlarnmoVmemyl1-N-f4-methoxv-7-morpholin-4-yl-
benzotbiazol-2-yI)->"pn7jimide
Using 4-chloro-3-chlororaethyl-benzoyi chloride and 2~memoxy-ethylamine the title
compound was prepared using die general procedure C as off-white solid (69 %), MS:
m/e=491(M+H+).
Example 283
4-Chloro-N- f 4-memoxy-7-moiphoIm4-yl-benzomiazoI-2-yl)-3-pvrrolidm-1 -vimethvi-henzamide

Using 4-chloro-3-cbloromethyl-benzoyl chloride and pyrroKdine the title compound was prepared using the general procedure C as light yellow solid (72 %), MS: m/e= 487 (M+fT).
Example 284
1 - f 4-f 4-Benzyloxy-7-morpholin-4yI-ben2othiazol-2-vl(aibamoyl)-ben7y;l1 -pyridininm-
chloride
Using 4-benzyloxy-7-morphoh4-4-yl-faeri2otHa2oI-2-ylamineJ 4-chlorometh.yI-benzoyl
chloride and pyridine the title compound was prepared using the general procedure C as
white solid (80 %), MS: m/e= 538 (M*).
Example 285
3-Pluoro-N-f,4-methcocy-7-moTphoh44-yl-benzothiazol-2-4)4pvn-ohdin-1 -ylmethyi-
benzamide
Using 4-chIoromemyi-3-fluoro-benzoyl chloride and pyrrolidine the title compound was
prepared using the general procedure C as yellow solid (25 %), MS: m/e= 471 (M+H*).
Example 286 3-T (2-Methoxy-e&7k™4)-™fttb.yri -N-(4-metboxv-7-morpholin-4r-vl-~berantKia7.ftU2-.
yl)-h»n7amiHp
Using 3-chloromethyl-ben2oyl chloride and 2-methoxy-emylamine the title compound was prepared using the general procedure C as light yellow solid (68 %), MS: m/e= 457
(M+H*). •
Example 287
3-W2-MethoCT-emyiymemvl-aTriinol-memyi4
benzothiazol-2-yl)-4enzamide
Using 3-chloromethyl-benzoyl chloride and (2-methoxy-ethyl)-methyl-airnne the title
compound was prepared using the general procedure C as yellow solid (75 %), MS: m/e=
471 (M+-H*).
Example 288
l-r4-(4-Me&o;4-7-morpholm-4-4benzothiazoI-24 chloride

Using 4-cHoromethyi-benzoyl chloride and pyridine the title compound was prepared using the general procedure C as white solid (33 %), MS: m/e= 462 (M*).
Example 289
N- (4-Memoxv-74morpholm-4-vl-benzothiaail-2-4"}-3-pvrroIi4in- 7 -yTmffthyj-hwigam ifo Using 3-chloromethyl-benzoyl chloride and pyrrolidine the title compound was prepared using the general procedure C as light yellow solid (65%), MS: m/e= 454 (M-t-H*).
Example 290
4- f (4-Emoxv-emyiaminoVraethyl ] -N-( 4-methoxy-7-morpho?Tn -4-yl-benzothiazol-2-yl)-
benzamide
Using 4-chloromethyI-benzoyl chloride and 2-emoxy-ethylarnine the title compound was
prepared using the general procedure C as white solid (18 %), MS: m/e= 471 (M+rf*").
Example 291
[R1-N-f4-Memoxy-7-morphoiin-4-yl-benzothiazol-2-yl44f3-memoxy-pyn4Hdin-l-yl-
methyD-benzamide
Using 4-chloromethyl-benzoyl chloride and [jRJ-S-methoxy-pyrroIidine the title
compound was prepared using the general procedure C as light yellow solid (18 %), MS:
m/e= 483 (M+H*).
Example 292
N-(4-Methoxy-7-morpholin4yi-benzothia?pl-2-yl4
Using 4-chloromethyl-ben2oyl chloride and methylamine the title compound was
prepared using the general procedure C as light yellow solid (63 %), MS: m/e= 413
(M+tT).
Example 293
f5l-N-(4rMe&oxy-7-morpholm-4-vl-benzothi
ylmetind)-benzarnide
Using 4-chloromethyl-benzoyl chloride and [S]-3-methoxy-pyrroUdine the title
compound was prepared using the general procedure C as light brown solid (13 %), MS:
m/e=483(M+H+).

Example 294
4-Azetidm-l-ylroemyl-N-(4-metfao:xy-7-mo
Using 4-chlorornethyI-benzoyl chloride and azetidine the title compound was prepared
using the general procedure C as light yellow solid (33 %), MS: m/e= 439 (M+rT*").
Example 295
4-fl-(2-Me&oxy-emylainmo)-etfayl1-N-(4-memo4
vl)-benzamide
Using 4-( l-chloro-ethyl)-benzoyl chloride and 2-methoxy-ethylamine the title compound
was prepared using the general procedure C as yellow solid (52 %), MS: m/e= 471
(M+fT).
Example 296
4-n-ff2-Methoxy-emyl)-mem\d-arnmo1-etfavll-N-(4-memoxT--7-morpholm-4-4-
benzothiazol-2-yll-benzamide
Using 4-(l-chloro-ethyi)-beriZoyl chloride and (2-methoxy-ethyl)-methyl-arnme the title
compound was prepared using the general procedure C as yellow solid (91 %), MS: m/e=
485 (M+rT).
Example 297
N7(4-Memoxy-7-morphoHn4yl-ben?ptbiazol-2-yl4-4-f 1-pvrrolidin-1 -yl-ethylV
benzarnide
Using 4-(l-chloro-ethyl)-benzoyi chloride and pyrrolidine the title compound was
prepared using the general procedure C as yellow solid (68 %), MS: m/e= 467 (M+H*).
Example 298
4-(2-Dimethvfeminr>ethylsulfanylmet44
benzothiazol-2-vl"l-benzamide
Using 4-chloromethyl-benzoyl chloride and 2-dimemylainino-ethanethiol the title
compound was prepared using the general procedure C as yellow solid* (52 %)> MS: m/e=
487 (M+H*).

Example 299
(roc) N-f4-Me1noxy-7-morpholin-4-yl-berizotiiia2oi-2-yi)-4-(fmetn4-f4T4,4-trifluoro-3-
hydroxy-huty1)-amino1-roeuiYll-beiizaniide
Using 4-chloromethyi-benzoyl chloride and (roc)-1,1,1 -trifiuoro-4-methylamino-butan-2-
ol the title compound was prepared using the general procedure C as white solid (89 %),
MS: m/e= 539 (M+rT).
Example 300
4-|[Etfayl-f2-memoxv-emvlVaniino1-meth4l-N-f4-methoxv-7-morpholig-4-yl-
benzotmazol-2-yl)-benzainide
Using 4-cmoromethyl-benzoyl chloride and (2-methoxy-ethyl)-ethyl-amine the tide
compound was prepared using the general procedure C as light brown solid (62 %), MS:
m/e=485(M+rT).
Example 301
4-4f2-Emoxy-emylVeth\4-anu4ol-memvn-K-f4"memoxv-7-morphoIin-4-4-
hpn7Athia?ol-2--yl)-benzairiide
Using 4-chloromethyl-benzoyl chloride and (2-ethoxy-ethyI)-ethyi-aniiiie the title
compound was prepared using the general procedure C as light brown solid (66 %), MS:
m/e=499(M+H*).
Example 302
3-Huoro4W2-meikoxy-e&ylVmethyl-airimo1-4
yl-benzothiazol-2-yl"l-ben2amide
Using 3-fluoro-4-chIoromethyI-ben2oyi chloride and (2-methoxy-ethyI)-methyi-amine the
title compound was prepared using the general procedure C as light brown solid (52 %),
MS: m/e= 489 (M+H*).
Example 303
4-lfBis-f2-emoxv-etnvi)-ainmo1-memyl4N-lf4-
2-yO-benzamide
Using 4-chloromethyl-benzoyi chloride and bis-(2-emoxy-ethyi)-amine me title
compound was prepared using the general procedure C as light brown solid (49 %), MS:
m/e=543(M+H+).

Example 304
4-lff2-Emoxy-etii4Vmeth.)d-ammo]-met3i4}-N-f4-memoxy-7~morpholin-4-4-
benzotfaiazol-2-yiVbenzamide
Using 4-chloromethyl-benzoyl chloride and (2-emoxy-ethyl)-memyI-arnine the title
compound was prepared using the general procedure C as white solid (78 %), MS: m/e=
485 (M+rT).
Example 305
N-( 4-Memoxv-7-mnrplin1in-4-vi-benzothiazoI-2-yi")-4-f 4-methoxy-pip eridin-l -yl -
methvD-benzamide
Using 4-chloromethyl-benzoyl chloride and 4-methoxy-piperidine the title compound was
prepared using the general procedure C as white solid (33 %), MS: m/e= 497 (M+H*).
Example 306
4-Diethyla minompthvl-N- (4-methoxy-7-morpholm-4-vi-benzothia2ol-2-vi yhmramiAr Using 4-clilorometh.yl-benzoyl chloride and diethylamine the title compound was prepared using the general procedure C as light yellow solid (64 %), MS: m/e= 456 (M+H*).
Example 307 4-f(2-Methoxy-ethy1ammoVmemyll-N-f4-mefooxv-7-m
Using 4-chloromethyl-benzoyl chloride and 2-memoxy-ethylarnme the tide compound was prepared using the general procedure C as white solid (64 %), MS: m/e= 457 (M+H*).
Example 308
N-{4-Mefooxy-7-morpholm-4-vi-benzotfoazol-2-yD-44
benzamide
Using 4-chloromethyl-benzoyl chloride and 2-methyl-lH-imidazole the title compound
was prepared using the general procedure C as white solid (87 %), MS: m/e= 464 (M+H*).
Example 309
N-(4-Memoxy-7-momhoHn-4-4-ber4othiazol2-Yl)-4-f4-4 b**n?anwjk*

Using 4-chloromethyi-benzoyl chloride and 1-methyl-piperazine the title compound was prepared using the general procedure C as white solid (78 %}, MS: m/e= 482 (M+H*).
Example 310
N-(4-Memoxy-7-moipholm-4-yl-ben2ntiiia2X>I-2-yl4
Using 4-chIoromethyi-benzoyi chloride and pyrrolidine the title compound was prepared
using the general procedure C as white solid (81%), MS: m/e= 454 (M+H*).
Example 311
N-f4-Metfaoxy-7-moTph™K"4-yi-benzotniazol-2-ffi
Using 4-chloromethyl-benzoyl chloride and morpholine the tide compound was prepared
using the general procedure C as white solid (83%), MS: m/e= 469 (M+H*).
Example 312
N-(4-Ber4loxy-7-morpholfo4-yl-benzotliiazol-2-ylM-44
amino] -methvlt-benzamide
Using N-(4-benzyloxy-7-morpholm4yl-benzotn4
and (2-memoxy-ethyl)-methyl-ainine the title compound was prepared using the general
procedure C as white solid (69 %), MS: m/e= 547 (M+lT).
Example 313
N-(4-Metfaoxy-7-morpholm4-Yl-benzothia2ol-2-4 ammol-methyll-benzamide; hydrochloride N-(4-Methoxy-7-morphofo4-yI-benzothiazaI-2-yl)4-4
{100 mg> 0.24 mmol), triethylamine (35 mg, 0.34 mmol), potassium iodide (0.4 mg, 0.02 mmol) and 333-trifluoro-rnropylaniine (48 mg, 0.27 mmol) were dissolved in ethanol (1 ml) and dioxane (0.5 ml). The reaction vessel is sealed and heated to 90°C for 18 h. Workup and purification as described in the general procedure C afforded the tide compound as light brown solid (28 %), MS: m/e= 509 (M+tT).
Example 314
4-(2-Memoxv-ed4xvmedivlVN-(4-memoxv-7-morpholm4vl-benzothiazol-2-4d)-benzamide

4-L4aromemyl-N-(4-methoxy-7-morpaoIm-4-yl-bei4 (200 mg,
0.48 mmol) and sodium hydride (42 mg 55 % dispersion in mineral oil, 0.96 mmol) were dissolved in 2-methoxy-ethanol (3.8 ml, 48 mmol) and stirred at ambient temperature for 18 h. Workup and purification as described in the general procedure C afforded the title compound as white solid (70 %), MS: m/e= 458 (M+H+).
Example 315
4-Memoxvrnem4-N-(4-memoxy-7-moipholm4-yl-b£n2othiazol-2-yl)-bfflMrniH4 4-C4oromethyl-N-(4-methoxy-7-morpholm4-yI-beri2omiazol-2-yl)-benzamide (200 mg, 0.48 mmol) were suspended in THE (5 ml) and sodium methoxide (0.27 ml 5.4 M in MeOH, 1.4 mmol) were added at 0 °CThe mixture was stirred at ambient temperature for 18 h. Workup and purification as described in the general procedure C afforded the title compound as light yellow solid (41 %), MS: m/e= 414 (M+H*).
Example 316
N- f 4-Methoxv-7- (l-oxo-lX4-thiomorpholm-4-Ti)-benzothiazol-2-,yll-heTi7aTnidf? To a solution of N-(4-memoxy-7-thiomorpholm4-yl-ben2othia2oI-2-yi)-beraamide (80 mg, 021 mmol) in [l,4]dioxane (3 ml) was added sodium periodate (89 mg, 0.42 mmol) and the mixture stirred for 20 h at ambient temperature. To this mixture water (10 ml) and dichloromethane (10 ml) were added, the phases were separated and the aqueous layer extracted twice with dichloromethane. The combined organic extracts were dryed with Na2S04 and the solvent evaporated. Recrystallization from hot THF afforded the title compound as white solid (21 %), MS: m/e= 402 (M+rT).
Example 317
N-U-MetbnYY-7-thiomorpholin-4-Yi-ben7.nt>iia7.ol-2-vl")-benzamide Following the general method of example 403 the title compound was synthesized from 3-(2-memoxy-5-miomorphoHn-4-yl-phenyl)-tmourea (synthesized from 4-bromo-l-memoxy-2-nitro-benzene and thiomorpholine as described for l-benzoyl-3-(2-methoxy-5-morpholin-4-yl-piienyl)-thiourea) as a white solid (15 %), MS: m/e= 386 (M+H*").
Example 318
5-Medivi-thiophene-2-carbpxylic acid (4-methoxy-7-piperazin-l-yl-hpn7irthiazol-2-yi)-amide

To asolution of4-{4-memoxy-2-[(5-methyl-tHophene-2-caibonyi)-aniino]-benzothiazol-7-yl}-piperazine-l-carboxyl£c acid benzyl ester (300 mg, 0.57 mmol) in dichloromethane (5 ml) were added boron trifluoride diethyl etherate (0.72 ml, 5.7 mmol) and ethane thiol (1.2 ml, 17 mmol) and the mixture stirred for 36 h. The volatile components are evaporated and the residue codistilled twice with toluene. The residue was dissolved in dichloromethane (25 ml), extracted with IN aqueous sodium carbonate and the organic phase dryed with NajSO* Removal of the solvent and flash chromatography (silica, eluent CHzCb/MeOH/aqu. NH4OH 100:10:1) afforded the title compound as light yellow solid (58 %), MS: mJe= 389 (M+H+).
Example 319
5-Methyl-tbinphene-2-carboxvlic acid [7-("4-acetyl-pipera2in-l-vl)-4-metho%y-benzomiay-ol-2-vll -amide
5-Methyl-truophene~2-carboxylic acid (4-methoxy-7-piperazm-l-yi-benzotlnazol-2-yl)-amide (100 mg, 0.26 mmol) were suspended in DMF (2 ml) and treated with acetyl chloride (22 \A, 0.30 mmol) and pyridine (27 ul, 0.34 mmol) and the mixture stirred for 5 h at ambient temperature. Workup and purification as described in the general procedure C afforded the product as a white solid (55 %), MS: m/e= 431(M+H*).
Example 320
4-{4-Memoxv-2-[f5-memvl-thiophene-2-caThnTiy14ammn]-hpn7otihiazn]-7-vll-pippra7ine-l-carboxvlic acid methyl ester
Using methyl chlorofbrmate the tilte compound was synthesized as described for example 319 and obtained as white solid (26 %), MS: m/e= 447(M+H+).
Example 321
5-Methvi-thiopbene-2-carboxylic acid [4-methoxy-7-f4-methyl-piperawn-l -vD-benzothiazol-2-yn -amide
To a solution of 5-methyl-tbiophene-2-carboxylic acid (4-methoxy-7-piperazhi-l-yi-benzothia2ol-2-yl)-arnide (100 mg, 0.26 mmol) in methanol (8 ml) were added formic acid (100 ul, 2.6 mmol) and formaldehyde (23 ul, 0.31 mmol) and the mixture refluxed for 18 h. Workup and purification as described for 5-methyl-thiophene-2-carboxyiic acid (4-memoxy-7-prperazm-l-yI-benzothiazol-2-yi)-arnide afforded the product as light yellow powder{34-%), MSrrak«=4f»(14+*f1">.

Eyaaspte-323
5-Methyl-tbJophene-2-carbogidic acid \ 7-f2,3-dihvdro-lH-indol-6-yl)-4-inetlioxy-
ben7othta?oi-2-yi 1-amide
The tide compound was prepared from 5-methyl-thiophene-2-carboxylic acid (7-iodo-4-
memoxy-benzothiazol-2-yl)-amide (100 mg, 0.23 mmol) and 6-iodo-23-dihydro-lH-
indole using the general procedure B in Example 54 as light brown crystals (26 %), MS:
m/e=422(M+Hf).
Intermediate
4r(4-Beri24oxv-3-nitro-phenYl)-rnorpb.oline
The tide compound was prepared using morpholine and l-benzyloxy-4-bromo-2-mtro-benzene (prepared from 4-bromo-2-nftro-anisol and benzyl bromide) using the general method of example ""4-(4-memoxy-3-nitro-phenyI)-morpholinen as yellow solid (58 %\ MS: m/e= 315(M+H+).
Intermediate
?.- A mini->-4-morphnHTi-4-yl-phenol
Catalytic hydrogenation of 4-(4-benzyloxy-3-nitro-phen"yl)-morpholine (5 g, 16 mmol) in dichloromethane (500 ml) and ethanol (500 ml) using palladium on carbon (500 mg, 10%) afforded the title compound as a grey solid (96 %), MS: mVe= 194(M+).
Example 323
N-f4-HydroxyT7-rnnTpbolin-4-vi-beri20thiazol-7.-y1)-KpTi7aTTii4p The title compound was prepared using 2-arriino--4-morpholin-4-yl-phenol as described for N-(4~rnethoxy-7-morpholm4yl-benzothiazol-2-yl)-benzamide and obtained as a light brown solid in 14 % overall yield, MS: m/e= 356(11+11*).
Example 324
5-MedwJ-thiophene-2-carboxyHc acid f7-f3-dimethy1amir>f>-pyiTolidip-l-yl)-4-methoxy-benzothiazoI-2-yi] -amide
Using 5-methyI-thiophene-2-carbonyl chloride and 7-(3-dimethylamino-pyrrolidui-l-yl)-4~methoxy-ben2X)thiazol-2-yl-amine the tide compound was prepared using die general method of example 1 as yellow solid (90 %), MS: m/e= 417 (M+fT).

Intermediate 7- (3-Dlmethylamino-pyrroudin-1 -vl44methoxv-t)enzothia7Jol-2-yl--amine Following the general method of example 403 the title compound was synthesized from [5-(3-dimemylarm4o-ptyrrolidin-l--yl)-2-methoxy-phenyl] -thiourea (synthesized from 4-bromo-l-methoxy-2-nitro-benzene and dimethyI-rjyrrou"dm-3-vl-arnine as described for (2-methoxy-5-morpholin-4-yl-phenyl)-thiouxea) as a white solid (25 %), MS: m/e= 293 (M+rT).
Example 325
Tetrah.ydro-pvran-4-carboxyIic acid f4-methoxy-7-morpholin-4-yl-benzothiazol-2-ylV amide
To a solution of 2-anuno4memoxy-7-morphoIm-4r-yl-benzothia2ol (100 mg, 0.4 mmol) in tetrahydrofiirane (2 ml) were subsequently added N-emylniiisopropylamine (194 Q, 1.1 mmol) and tetrah.ydropycan-4-caibonyl chloride (77 mg, 0-52 mmol, dissolved in 0.5 ml tetrahydromrane) and the mixture refluxed for 3 h. The mixture was then cooled to 0°C methanol (0.4 ml) was added and the mixture slowly warmed to 20 *C. Then the mixture was evaporated to dryness, dichloromethane was added (3 ml) and extracted with saturated aqueous sodium carbonate. After back extraction of the aqueous phase with two portions of dichloromethane (3 ml), the combined organic phases were dryed with Na2S04 and the solvent evaporated. The crude product was was then chromatographed over SiO4 eluting with CH2Q2/MeOH 98:2, the product fractions were pooled and the solvent evaporated, to afford the title compound as a beige powder (142 mg, 76 % yield), MS: m/e= 378(M+H+).
Following the general method of example 325 the following examples were prepared
Example 326
4-(4-Memoxy-7-morpholm4yl-benzothia2oI-2-vlcart
acid tert-butyi ester
Using 2-ammo-4-memoxy-7-morphoIm-4-yi-benzothiazoI and 4-chlorocarbonyI-
piperidine-1 -carboxylic acid tert-butyl ester the title compound was obtained as a white
solid (3 %), MS: m/e= 477(M+rT).
Example 327
l-Acetyl-piperidine-4-carboxviic acid f4-melhoxy-7-moipholm-4-vl-benzothiazol-2-vl)-amide

Using 2-amino-4-methoxy-7-moipholin-4-yl-benzothiazol and l-acetyl-piperidine-4-carbonyl chloride the tide compound was obtained as a white solid (22 %), MS: m/e= 419(M+rT).
Example 328
Piperiduie-4-carboxyiic add (4-methoxy-7-morpholin-4-vl-ben2othiazol-2-vi)-.atntHf 4- (4-Methoxy-7-moipholm4-yl-beriZotbiazol-2-ylcarbamoy!)-piperidine-l -carboxylic add tert-butyl ester (95 mg, 0.2 mmol) were dissolved in trifluoroacetic add (0.8 ml). After 1 h at room temperature, the mixture was evaporated to dryness. Purification as described for tetrahydro-pyran-4-carboxylic add (4-metboxy-7-morphoh44yl-benzotbiazol-2-yl)-amide afforded the title compound as a white solid (77 %), MS: m/e= 377(14+14).
General procedure E (ureas): The appropriate substituated 2-amino-benzothiazol (1 part, typically 500 mg) is dissolved in CH2CI2 (100 parts) and treated with pyridine (3 parts) and phenyl chloroformate (1.25 parts). After stirring for 30 min at room temperature the mixture is remixed for 2 h when the appropriate amine (5 equivalents) is added. After refluxing for 18 h, the mixture is evaporated to dryness, dissolved in CH2Q2 and extracted with aqueous sodium carbonate, after back extraction of the aqueous phase with CH2O2 the combined organic layers were dried with NaaSO*, and evaporated to dryness. The product is isolated by flash chromatography (silica, eluent dichloromethane containing 23 % methanol).
Following the general method E the compounds of examples 329 to 367 and Example 370 were prepared
Example 329
4-r(4-HuorcH-phenvIammo)-methvl1-piperidine-l-carboxylicaddf4-methoyy-7-
morphoh4n"4--yl--benzothiazoI-2-yI)-arnide
Using 4-memoxy-7-morpholm-4-yl-ben2otbia2ol-2-ylamine and 4- [(4-fluoro-
phenyiamino)-methyl]-piperidine the title compound was obtained as off-white solid (25
%). MS: m/e= 522 (M+H*).
Example 330 4rHydrQxymethy4-4-phenvi-pip4ridinp-1 -carboxylic add f4-methoxy-7-morphfilin-4-vl-

Using 4-meliiosy-7-morpholin4yl-beiKotiu4ol-2-yiainiiie and 4-hydroxymethyl-4-phenyi-piperidine the title compound was obtained as light yellow solid (50 %). MS: m/e= 483 (M+H+).
Example 331
f l-("4-Methoxy-7-moi4holm4-yl-benzQthiazoi-2-yi-carbaiHoyl )-piperidi*n-4-ylTnet4y{ ] -
carbaroic acid metbyl ester
Using 4-memoxy-7-moiphottn-4-yl-benzotm4ol-2-yl-amine and piperidin-4-yhnethyl-
carbamic acid methyl ester the title compound was obtained as white solid (81 %). MS:
m/e=464(M+H+).
Example 332
4-Ethvl-piperidine-l-carboxvlic acid f4-methoxy-7-morpholin-4~yi-benzomiazol-2-yi)-amide
Usnlg4-methoJ4-7~mo4phoIm-4-yJ-be42X)tm"a2o42-yianline and 4-ethyI-piperidine the title compound was obtained as white solid (26 %). MS: m/e= 406 (M+H*).
Example 333
4-(2-Oxo-pvrroHdin-l-yhTiethyl4-piperidine-l-carboxylic add (4-methoxy-7-morpholin-
4-yl-benzothiazol-2-yiVamide
Using 4-methoxy-7-morpholm4-yi-benzotiiazol-2-yl-amine and 4-(2-oxo-pyrroHdin-l-
yimethyi)-piperidine the title compound was obtained as white solid (29 %). MS: m/e=
474 (M+H1");
Example 334
4-(2-Methoxy"ethyl)-pipera7ine-l-cafboxyUc add (4-methoxy-7-morpholin-4-yl-hf>n7.nthinzoU2 -yP-amide
Using 4-methoxy-7-morphonn4yl-benzotmazol-2-yl-aiiiine and 4-(2-methoxy-ethyl)-piperazine-the title compound was obtained as off-white solid (79 %). MS: m/e= 437
(M+H+).
Example 335
4-Cranometfa4-piperidme-l-carbox4ic acid (4-metiioxr-7-morpholin-4-yi-bena3thiazol-2-vJ")-amide

Using 4-memoxy-7-morphoiin4yi-ben20thiazol-2-yl-amine and 4-cyanomethyl-piperidine the title compound was obtained as white solid (46 %). MS: m/e= 416 (M+H1").
Example 336
[ 1-f 4-MethoCT-7-morpholin44-benzothia2ol-2-4Karbanio4)-piperidin4TdmetfaTrfl -carhapic acid tert-butyl ester
Using 4-memoxy-7-morphoh44-yI-benzothiazoI-2-yl-amine and piperidin-4-ylmethyI-caibamic acid tert-butyl ester the title compound was obtained as white solid (11 %). MS: m/e= 506 (M+H*).
Example 337
4-f2-f"4-CbJoro-phen}dVtetiahydro"njran-241-piperidine4l 7-morpholin-4-yl>ben7fithia7.ol-2-yl")-aniide
Using 4-methoxy-7-morphoh44yl-benzo1m4zol-2-yl-aniine and 4-[2-(4-chloro-phenyl)-
tetrahydro-f«xan-2-yl]-piperidine the title compound was obtained as white solid (43 %).
MS:m/e=557(M+H+).
Example 338
4-(2-Hydroxv-edi4)-piperidine-l-carboxylic acid f4-merooxy-7-morpholin-4-Tl-benzothrazoJ-2-vi )-amide
Using 4-memoxy-7-morpholm4yl-benzomiazol-2-yl-amine and 4-(2-hydroxy-ethyl)-piperidine the title compound was obtained as white solid (64 %). MS: m/e= 421 (M+H*).
Example 339
l-(2-Mefoo:xy-emylV34f4-memoxy-7-morpholm44
Using 4-methoxy-7-morpholm4yl-benzotbia2ol-2-yl-amine and (2-methoxy-ethyl)-
methyi-amine the tide compound was obtained as white solid (65 %). MS: m/e= 381
(M+H*).
Example 340
4-Methoxyacetvi-piperazine-1-carbo3iylic acid f4-methoxv-7-morpholin-4-Ti-
benzot4ia7J)l-2-yl1-amide
Using 4-methoxy-7-morpholm4yl-ben20thiazol-2-yl-amine and 4-methoxyacetyl-
piperazine the title compound was obtained as beige solid (84 %). MS: m/e4 450 (M+H*).

Example 341
4-Methvi-pippn, amide
Using 4-metiioxy-7-morphoIm-4-yi-faenzothiazoI-2--yl-annne and 4-methyl-piperidine the
title compound was obtained as white solid (47 %). MS: m/e= 391 (M+H*).
Example 342
4-Oxo-piperidine-l-carboxviic acid (4-methoxy-7-morpholin-4-4d-benzothiazol-2-vD-
arnitfe
Using 4-methoxy-7-moipholm-4-yl-benzotniazol-2-yI-ainine and piperidin-4-one the title
compound was obtained as white solid (38 %). MS: m/e= 391 (M+fT).
Example 343
4-Cydopropyl-4-hydroxy-piperidine-l-carboxviic acid C4-methoxy-7-morphoHn-4-yl-
benzothiazol-2-yi)-amicie
Using 4-meliioxy-7-moi7hoIm4-)4-beiizothiazol-2-7l-amine and 4-cyclopropyi-4-
hydroxy-piperidine the title compound was obtained as white solid (27 %). MS: m/e= 434
(M+iV).
Example 344
l.I-Dioxo-l4-thiomorphol4f-4farboxylic acid (4-methoxy-7-morpholin-4-yi-
benzothiazol-2-yl")-amide
Using 4-methoxy-7-morpholm-4-yl-ben20tbiazol-2-yl-ainine and tbiomorpholine 1,1-
dioxide the title compound was obtained as white solid (50 %). MS: m/e= 427 (M+H*).
Example 345
4-HvdroxvmethyI-piperidine-l-carboxvu"c acid t4methoxy-y-morpholin4-yl-
benzothia7r>1-7.-yl"l-amiHe
Using 4-melkoxy-7-morphoUn-4~yl-benzoliiiazol-2-ylamine and 4-hydioxymetbyi-
piperidine the title compound was obtained as white solid (31 %). MS: m/e= 407 (M+H1-).
Example 346

Octahydto-quinoline-l-caiboxyiic acid (4-methoxv--7-morpb,olin-4-yl-benzothiazol-2-ylV
amide
Using 4-metho4-7-inorphQUn4yi-benzo1ii4ol-2-yl-amine and octahydro-quinoline the
tine compound was obtained as white solid (79 %). MS: m/e= 432 (M+K1-).
Example 347
2.3-Benzo-1.4-dioxa-8-a2a-spiror4.5ldecane-8-carboxvdic acid f4-methoxv-7-moTphnliTi-
4-yl-benzothiazol-2-yl)-amide
Using 4-methoxy-7-morpholin4yl-benzotinazol-2-yl-amine and 2,3-benzo-l,4-dioxa-8-
aza-spiro[4,5]decane the tide compound was obtained as white solid (63 %). MS: m/e=
483 (M+H*).
Example 348
4-f 4-Metfaosy-7-g]orpIioJin-4-v3-benzomiazo]-2-vi-carbamoy] )-piperazme-1 -carboxyiic
acid methyl eyter
Using 4-methoxy-7-morpbolin4-yl-benzothiazol-2-yl"amine and piperazine-1-carboxyfic
acid methyl ester the title compound was obtained as white solid (90%). MS: m/e= 436
CM+H*).
Example 349
Octahvdr"-i"!rtq»"noline-2-carboxylic acid f4-methoxy"7-morpholin-4-yl-benzothiazol--2-
yl)-amide
Using 4-methoxy-7-moipholin4yl-benzotbiazol-2-yl-amine and octabydro-isoquinoline
the title compound was obtained as white solid (53%). MS: m/e= 432 (M+H*).
Example 350
3-Methyi-piperidine-l-caiboxylic acid (4-methoxy-7-morphoIin-4-yl-hen7nfhia7ol-2-yl)-
amide
Using 4-memoxy-7-mc4holm4yl-benzounazol-2-yl-aniine and 3-methyl-piperidine the
title compound was obtained as white solid (50 %). MS: m/e= 391 (M+H1").
Example 351
3-HvdroxymethTi-piperidine-l-carboxvlic acid f4-memoxy-7-morpholin-4-yl-benzothiaanl -2-yl)-aTnide

Using 4-methoxy-7-morphoIm-4~yl-benzothiazoI-2-ylaraine and 3-hydroxymethyl-piperidine the title compound was obtained as white solid (69 %). MS: m/e= 436 (M+H*).
Example 352
3>4-Benzo-l~oxa-8-aza-spiio[4.5]decane-8-carboxyiic acid f4-methoxy-7-mnrphnlin-4-vl-benzothiazol-2-vl-amide
Using 4-metbxixy-7-morpholm-4-yl-benzotiuazoI-2--yl-amine and 3,4-benzo-l-oxa-8-aza-spiro[4.5]decaue the title compound was obtained as light yellow solid (67 %). MS: m/e= " 481 (M+H*).
Example 353
4-(4-Methoxy-7-morpholin-4-yl-benzomiazoI-2-yl-carbamov1 4-pipwazine- l-carboxylic
acid tert-bntvi ester
Using4-methoxy-7-moipholm-4-yl4>enzotMazol-2-yl4
acid fert-butyl ester the title compound was obtained as light yellow solid (66 %). MS:
m/e= 478 (M+H1").
Example 354
4-Hvdroxv-4-phenY4-piperidine-l-carboxylic acid f4-methoxv-7-morpholin-4-yl-
benZ0tbia7n1-?--v11-amidft
Using 4-methoxy-7-mcopholm-4-yl-benzot3iiazol-2-yl-aniine and 4-hydroxy-4-phenyl-
piperidine the title compound was obtained as light yellow solid (36 %). MS: m/e= 469
(M+H*).
Example 355
4-Methyi-piperazine-l-carboxylic acid (4-memoxy-7-morpholin-4-yl-ben2othiazoI-2-viV
amide
Using 4-rnethoxy-7-morpholm-4-yl-benzotbJaMl-2-yl-ainine and 4-methyl-piperazine the
title compound was obtained as beige solid (20 %). MS: m/e= 392 (M+H1").
Example 356
4-Trifluorometh4-pippridine-l-carboyylic acid f4-methoxv-7-morphoIin-4-yl-
benzotbTa7r>l-2-yl)-aTnidp
Using 4-methoxy-7-morpholm-4-yl-berizotiua741-2-yl-amine and 4-trifIuoromethyI-
piperidine the title compound was obtained as white solid (16 %). MS: m/e= 445 (M+H4").

Example 357
f l,4"1Bipiperidmyl-l"-carboxylic acid f4-methQJCV-7-morphnlTn-4-yl..benzothiazol-2-ylt-
amide
Using 4-metJaoxy-7-moi4holin4yl-benzothiazol-2~yl-amine and [l,4"]bipiperidinyl the
title compound was obtained as white solid (35 %). MS: m/e= 461 (M+H*).
Example 358
3-(4-Methoyy-7-morpholiD-4-vi-benzothiazoI-2-4V 1- (4-methoxy-phenyO- 1-methyi-urea Using 4-metho4-7-morphoUc-4-yl-benwtliiazol-2-yi-amine and 4-methoxy-phenyl}-methyl-amine the title compound was obtained as light yellow solid (40 %). MS: m/e= 430 (M+JT).
Example 359
L4-Diosa-8-aza-spiror4.5ldpraDe-8-carbox)dicaddf4-methoxv-7-moi7jbrt1in-44yl-beazotbiazol-2-vD-amide
Usmg4-methoxy-7-moiphohn-4-yl-ben20thiazol-2-yl-amuie and l,4-dioxa-8-aza-spiro [4,5] decane the title compound was obtained as beige solid (28 %). MS: m/e= 435 (M+H1").
Example 360
3.4-Dihvdro-lH-isoquinoline-2-catboxylic acid (4-methoxv-7-morpholin-4-yl-
benzothiazol-2-yl)-amide
Using 4-methoxy-7-morpholm4yl-ben20tbJazol-2-yl-amine and 1,2,3,4-tetrahydro-
isoqumoline the title compound was obtained as orange solid (63 %). MS: m/e= 425
(M+fT).
Example 361
3-f 4-Methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-l -methyl-1 -phenyl-urea
Using 4-methoxY-7-morpholm-4-yl-benzotWazol-2-yl-anTine and methyl-phenyl-amnie
the title compound was obtained as white solid (19 %). MS: m/e= 399 (M+H1").
Example 362
4-Hvdroyy-piperidioe-l-carboxylic acid l"4-methoxy-7-morpholin-4-vl-ben7-ntliiazol-2-y?)-amiHg

Using 4-memoxy-7-moipholm-4-yl-benzothiazol-2-Yl-arnine and piperidin-4-ol the title compound was obtained as yellow solid (50 %). MS: m/e= 393 (M+H*).
Example 363
4-Memoxy-piperidine-l-carboxviic acid (4-methoxy-7-morpholin-4-yi-benzotbia2oI-2-
yl)-amide
Using 4-methoxy-7-morpholm4yl-beii20tbia2ol-2-yI-atDine and 4-methoxy-piperidine
the title compound was obtained as yellow solid (33 %). MS: m/e= 407 (M+H*),
Example 364
l-Oxo-ll4-thTQinorpholine4carboxylic acid f4-memoxy-7-moipholin-4-yl-hffn7.nthia7.nl-
2-vP-amide
Using 4-memoxy-7-morpholm-4-yl-benzothiazol-2-yl-ainine and thiomorpholine 1-oxide
the tide compound was obtained as white solid (87 %). MS: m/e= 411 (M+H*).
Example 365
Methanesulfonic acid l-(4-memoxy-7-moipholm-4-yl-benzothiazol-2-yIcarbamoTl)"
piperidm-4-yl-metbyi ester
4-Hydroxymethyl-piperidine-l-carboxylic acid (4-methoxy-7-morpholin-4-yl-
benzotbiazol-2-yi)-amide (300 mg, 0.43 mmol) andN-ethyldiisopropylamine (95 pi, 0.56
mmol) were dissolved in CH2Q2 (10 mi), mefhanesulfonyl chloride (36 ul, 0.47 mmol) was added and the mixture stirred at ambient temperature for 3 days. Purification as described in the general procedure E afforded the product as a white solid (34 %) MS: m/e= 466 (M+fT).
Example 366
Piperazine-1-carboxyiic acid f4-methoxv-7-morpholip-4-yl--beDzothia7nl-2-Yl)-3miHe Following the general method for piperidine-4-carboxyhc acid (4-methoxy-7-morphoUn-4-yi-beri7x)thiazol-2-yl)-amide the title compound was prepared from 4-(4-methoxy-7-rnorpholin-4-yl-benzo1hia2ol-2-yl-carbamoyl)-pipera2ane-l-carboxyHc acid tert-butyl ester as a light yellow solid (99 %).MS: m/e= 378 (M+H*).
Example 367
4-Aminomethyl-piperidine-l-carboxyUc acid (4-memoxy-7-morpholin-4-y4-b
Following the general method for piperidine-4-carboxylic acid (4-methoxy-7-morpholin-
4-yl-benzothiazol-2-yl)-amide the title compound was prepared from [l-(4-methoxy-7-
morpholm-4-yl-berizotmazol-2-yl-carbamoyl)-pipOT acid tert-
butyl ester as a white solid (50 %) JvIS: m/e= (M+H4").
Example 368
(4-Mefeoxy-7-morpholin4vl-benzothiazol--2-ylVcarbamic acid 2-methoxy-ethyl ester 4-Methoxy-7-mc«phonB4y/-berizotiuazof-2-yl-amme (300 mg, 1.1 mmof) and N-ethyldiisopropylamine (0.56 ml, 3.4 mmol) were dissolved in tetrahydrofurane (11 ml) and 2-methoxyethyl chloroformate (0.19 ml, 1.4 mmol) were added over 5 min. Then the mixture was heated to 70 °C for 3 h. The mixture was cooled to room temperature, water added and extracted twice with ethyl acetate. TRhe combined organic phases were dryed with Na2S04 and evapprated to dryness. The title compound was obtained as off-white solid (52 %). MS: m/e= 368 (M+H4").
Example 369
J.4- (4-Methoxv-7-morpholin-4-yl-benzothiazoI-2-yicarbamoT4)-benzyl] -methyi-carhaTnic
add methyl ester
N-(4-Memoxy-7-moi4hohn-4-yi-benzothiazol-2-4
(100 mg, 0.24 mmol), pyridine (29 ul, 0.36 mmol) and methyl chloroformate (24 jd, 0.32
mmol) were dissolved in dichloromethanel (5 ml) and stirred at ambient temperature for
18 h. Workup and purification as described in the general procedure C afforded the title
compound as light yellow solid (66 %), MS: m/e= 471 (M+fT).
Example 370
l-Oxo-lXj-thiomorpholine-4-carboxviic acid f4-memoxy-7-piperidm-l-yi-benzotbia2ol-2-vP-amide hydrochloride
Using 4-memoxy-7-piperidm-l-yl-benzouHa2»l-2-ylamine and tbiomorpholine 1-oxide the titie compound was obtained as white solid in accordance with general procedure E (80 %). MS: m/e= 409 (M+H*).
Example 371 N-(4~Emoxy-7-piperidm-l-vl-benzot+jia2ol-2-vlM-fluoro-ben2ajnide
The title compound was prepared strarting from 4-bromo-l-ethoxy-2-nitro-benzene and piperidine as described for 4-fluoro-N-(4-memoxy-7-morphoh4-4-yl-beri20thiazol-2-yI)-

benzamide (Example 275) and obtained as a yellow solid in 10 % overall yield, MS: m/e= 400 (M+H1").
Example 372
l-Huoro-N-(4-isopropoxy-7-piperidin-1 -y!-beiizotMazoI-2-yI)-hf»n?smirip
Ihe title compound was prepared strarting from 4-bromo-l-isopropoxy-2-riitro-benzene and piperidine as described for 4-fiuoro-N-(4-meaioxy-7-moiphoun4yi-benzothiazol-2-yl)-benzamide (Example 275) and obtained as a light brown solid in 10 % overall yield, MS: m/e= 414 (M+lT).
Example 373
4-Fluoro-N-(4-memoxy-7~pyrroHdin- l-yl-benzolhiazol-2-yl VhCTi7amiH The title compound was prepared strarting from 4-bromo-l-memoxy-2-nitro-benzene and pyrrolidine as described for 4-fluoro-N-(4-methoxy-7-morpholin-4~yI-benzothiazoI-2-y5)-benzamide (Example 275) and obtained as a light brown solid in about 10 % overall yield, MS: m/e= 372 (M+H+).
Example 374
4-Ruoro-N-f4-memoxy-7-[l,4loxazepan4yl-benzothia?ol-2-yiVbenMiniHf»
The title compound was prepared strarting from 4-bromo-l-methoxy-2-nitro-benzene and [1.4]Gxazepane as described for 4-fluoro-N-(4-memoxy-7-morpholin-4-yI-benzothiazol-2-yl)-benzamide (Example 275) and obtained as a light yellow solid in about 10 % overall yield, MS: m/e= 402 (M+H+).
Example 375
Morpholine-4-carboxyiic acid l4-memoxv-7-f4-methoxy-piperidin-l-vlVbenzo1hia2ol-2-yH -amide
The tide compound was prepared strarting from 4-bromo-l -methoxy-2-nitro-benzene and 4-methoxy-piperidine as described for morpholine-4-carboxylic acid (4-methoxy-7-morpholin-4-yl-ben2othia2ol-2-yl)-amide (Example 136) and obtained as a light yellow solid in about 10 % overall yield, MS: m/e= 407 (M+H+).
Example 376
N- (7-Azepan-1 -yl-4-methoxv-benzothiazol-27yl) -4-nrtro-benzamide
The title compound was prepared using 4bromo-l-met&oxy4-nitro-benzene, azepane and 4-nitro-benzoyl chloride as described for 4-fluoro-N-(4-methoxy-7-morpholin-4-yl-

benzothia2ol-2-yI)-benzamide (Example 275) and obtained as a light yellow solid in about 10 % overall yield, MS; m/e= 427 (M+H*).
Example 377 Morphnline-4-carboxvlic acid f4-methoxv-7-thiophen-3-yl-benzothiazol-2-Yl)-amide
The title compound was prepared strarting from 4-bromo-l-memoxy-2-nitro-benzene and trimethyl-thiophen-3-yl-staruiane as described for morphoIine-4-carboxylic acid (4-methoxy-7-phen)d-benzothiazol-2-yl)-amide (Example 157) and obtained as alight yellow solid in about 10 % overall yield, MS: m/e= 376 (M+H+).
Example 378 4-Fluoro-N- \ 4-methoxy-7- (2-methyi-irDidazoI- l-vlVbenzothiazol-2-yll -hwi?ami4
N-(7-Acetylann4o4methoxy-benzothia2ol-2-yl)4-fluoro-benzamide (100 mg, 0.28 mmol) and Lawessons reagent (135 mg, 0.33 mmol) were dissolved in THF (10 ml) and stirred at ambient temperature for 18 h. Removal of the solvent and flash chromatography (silica, eluent CH2Cy2N aqu. NH3 in MeOH 99:1 to 19:1) afforded a yellow solid which was dissolved in acetone (10 ml) and treated with iodomefhane (19.8 mg, 1.4 mmol). After 3 h at ambient temperature the solvent was removed and after dissolution in ethanol (10 ml), aminoacetaidehyde dimethyl acetal (15 mg, 1.4 mmol) were added and the mixture stirred for 18 h at room temperature. The solvent was removed and the residue refluxed for 24hin ethanol (10 ml) and cone sulfuric acid (1 ml). Theniixture was diluted with, water (50 ml) and the pH adjusted to 8 with sodium carbonate. It was extracted three times with dichloromethane. The combined organic extracts were dryed with sodium sulfate and the solvebt removed. Flash chromatography (silica, eluent CH2CI2/2N aqu. NH3 in MeOH 96:4 to 9:1) afforded the title compound as brown solid, MS: m/e= 383 (M+rT).
Example 379
2-Chloro-N-(4-memoxy-7-morpholm-4-yi-bgr4
To a stirred suspension of 4-metJioxy-7-morphoh44yl-benzothiazol-2-yl-amine (13.3 g, 50.1 mmol) in THF (700 ml) was added JV-emyldiisopropylamine (21.3 ml, 125 mmol). The mixture was then cooled to 5 °C and a solution of 2-chloro-6-methyl-isonicotinoyl chloride (10.5 g, 55.1 mmol) in dichloromethane (350 ml) was added dropwise over 2 hours. The reaction mixture was then stirred overnight at 20 °C. To this mixture was added r4ffthflTini (4Q ml) and gtirr-ipj. mjmitps. Tie mixture,was. then, concentrated in vacuo and the residue partitioned between ethyl acetate and saturated

sodium bicarbonate solution. The organic phases were then dried over NajSCU and the solvent evaporated. The crude product was then chromatographed over SiC>2 (Merck 230-400 mesh) eluting with CH2CyMeOH (98:2), the product fractions were pooled and the solvent evaporated, to afford the title compound as a brown solid (16.0 g, 76 % yieid)s MS: m/e = 421 (MfdJ+H*), 419 (M4CIJ+H*).
Following General Procedure E the compounds of examples 380 and 381 were prepared
Example 380
(4-Methoxy-7-morpholin-4-vl-benzotluazol-2-yl)-urea
Using 4-me1ioxy-7-morpholm-4-yl-benzothia2ol-2-yl-aiMine and ammonia the title compound was obtained as a white solid (20%), MS: m/e = 309 (M+H4).
Example 381
(4-Memo34-7-morpholm-4r-vl-b€nzothiazoI-2-Yl)-rarhamif: acid phenyl ester
Using 4-metboxy-7-morpholm-4yl-beiizothiazol-2-yl-arnine and without adding an amine the title compound was obtained as a white foam (75%), MS: m/e s 386 (M+H*).
Following the general method of example 379 the fallowing compound was prepared
Example 382
2-Cmoro-N-f4-meraoxy-7-morpholm-4-vl-benzot4
Using 4-methoxy-7-morpholm-4-yl-benzotliiazol-2-yl-arriine and 2-chloro-isonicotinoyl chloride the title compound was obtained as a brown solid (59%), MS: m/e = 407 (Ufa}+H*)t 405 Example 383
2-Iodo-N-(4-methoxv-7-morphnlin-4-Yl-benzotbia7n1 -?.-yl )-6-methyi-isonicotinamide
To a stirred suspension of 2-cMoro-N-(4-methoxy-7-morpholm4yl-benzothiazol-2-yl)-6-methyl-isonicorinamxde (1.00 g, 239 mmol) in ethyl methyl ketone (10 ml) and dioxane (20 ml) were added sodium iodide (2.0 g, 13.3 mmol) and hydriodic acid (0.95 ml, 7.2 mmol, 57 % aqueous). The mixture was then beated at 100 "C for 96 hours. The mixture was then concentrated in vacuo and the residue resuspended in dichlorornethane and washed sequentially with saturated sodium bicarbonate solution, 0.1M sodium tiuosulfate solution, and saturated brine. The organic pbate-mtbea dried over N*jSO» and the

solvent evaporated. The crude product was then chromatographed over SiCb (Merck 230-400 mesh) eluting with CH2a2/MeOH (99:1 then 98:2), the product fractions were pooled and the solvent evaporated, to afford the title compound as a brown solid (80 mg, 7 % yield), MS: m/e = 511 (M+rT).
Following General Procedure E the compounds of examples 384 and 385 were prepared
Example 384
1 -Benzyl-3-(4-meu4oxy-7-morphoIin-4-yl-benzothiazol-2-yI)-1 -methyl-urea
Using 4-methoxy-7-moipholm-4-yl-ben2X)thia2ol-2-yl-amine and N-benzylmethylanune the title compound was obtained as an off-white solid (94 %), MS: m/e = 413 (M+H1").
Example 385
3- (4-Memoxy-7-morphoUn-4-yl-benzothiazol-2-yl)-l -methyl- 1-phenethvl-uTfta
Using 4-methoxy-7-morpholm-4-yl-benzolnia2»l-2-ylamine and N-methyl-2-phenylethyiamine the title compound was obtained as an off-white solid (53 %), MS: m/e = 427 (M+H1-).
Following the general method of example 379 the compounds of examples 386 to 391 were prepared
Example 386
N-(4-Memoxy-7-moiphomi-4-vl-ben2othiazol-2-yl)-2-pb£nyI-acetamide
Using 4-methoxy-7-morplio]m-4-yl-ben2otbia2ol-2-yl-amine and phenylacetyl chloride the title compound was obtained as a light yellow soh"d (37 96), MS: m/e = 384 (M+H*).
Example 387
N"-(4-Memoxy-7-morphoIm-4-vI-benzothia2oI-2-yf)-Tff4Tw"r"r"arni"fIp
Using 4-medioxy-7-morphoh4-4-yI-benzotiu4zoI-2-yl-amine and propionyl chloride the title compound was obtained as alight yellow solid (5 %), MS: m/e = 322 (M+H*).
Example 388 2-Memoxy-N-f4-memoxv-7-morpholm-4-y4-km7rtthia2al-2-yl)-a«4mifi.-

Using 4-memoxy-7-morpholm-4-}d-benzothiazol-2-yI-amine and methoxyacetyl chloride the title compound was obtained as a light yellow solid (37 %), MS: m/e = 338 (M+H*).
Example 389 PfntaTinir acid f4-metiioxy-7-morpholin4yl-benzothia2ol-?-yl)-aTriiHp
Using 4-methoxy-7-morpholm-4-yl-benzo1iuazol-2-yl-amine and valeroyl chloride the tide compound was obtained as a light yellow solid (48 %), MS: m/e = 350 (M+H+).
Example 390
JV-(4-MetJioxv-7-morphouj4yi-benzothiazoi-2"yi)-isobutyramide
Using 4-methoxy-7-rnorpholm4yl-bemotbiazol-2-yl-amuie and isobutyryl chloride the tide compound was obtained as a light yellow solid (8 %), MS: m/e - 336 (M+H*).
Example 391
4-f4-Melhcc4-7-morphcJm4yl-benzotbia2ol-2"yl)-3-pheni6-Dropionarriide
Using 4-methoxy-7-morpholm-4-yl-benzolmazol-2-yI-ainine and 3-phenylpropionyl chloride the title compound was obtained as a light yellow solid (3 %), MS: m/e = 398 (M+H*).
Following General Procedure E the compounds of examples 392 to 396 were prepared
Example 392
l-Benzyl-3-(4-mellioxy-7-moipholin4yl-benzothiazol-2-ylVurea
Using 4-memoxy-7-morpholm-4-yl-benzothia2»l-2-yi-ainine and benzyiamine the title compound was obtained as an off-white solid (99 %), MS: m/e = 399 (M+H*).
Example 393
l:(4-Methoxv-7-moTpbolin-4-y1-hCT7.otMazol--2-,sd")-3-phenethyi-urea
Using 4-memo4-7-morpholm4yl-benzotbiazol-2-yl-amine and 2-phenylethylamine die title compound was obtained as an off-white solid (87 %), MS: m/e = 413 (M+H*).
Example 394
T-f2-Methoicv-emvlV3-f4-methcocv-7-moroholm-4--4-ben7nthia7.n1-7-yI)-VTr,

Using 4-methoxy-7-morpholin4-yl-benzotniazol-2-yl-arniQe and 2-memoxyethylamine the title compound was obtained as an off-white solid (80 %), MS: m/e = 367 (M+tF).
Example 395
1 -(2-DimethylamTTin-etbyI1-3-f 4-methoxv-7-morpholin-4-yl-benzothiazol-2-yl")-1-methyl-urea
Using 4-methoxy-7-moipholin4yl-benzolinazol-2-4yl-amiDe and WJOT-trimemylethylenediamine the title compound was obtained as an off-white solid (61 %), MS:m/e4394(M+H+).
Example 396
1 - (2-Dimemyiaminn-rthyl)-3-f 4-methoxy-7-rofirphnlin -4-yi-ben2otbiazQl-2-yl)-urea
Using 4-methoxy-7-morpholm-4-yl-benzothiazol-2-yl-arnine and 2-dimethylamino-ethyiamine the title compound was obtained as an off-white solid (79 %), MS: m/e = 380
(M+H1").
Following the general method of example 379 the compound of example 397 was prepared
Example 397 4-DimrtkylaTTimf>-W-f4-memo;jqr-7-morpholm-4
Using 4-methoxy-7-morphoun-4-yl-benzotaiazol-2-yi-amine and 4-dimethyiammo-butyryl chloride the title compound was obtained as a light yellow solid (10 %), MS: m/e = 379 (M+fT):
Preparation of intermediates for examples 1 to 187
Example 398
(7-Iodo-4-methoxy-benzotbiazol-2-ylVcarbamic acid methyl ester
(4-Metlioxy-benzoiiuazol-2-yl)-carbaraic acid methyl ester (31.0 g, 130 mmol) and sodium acetate (32.3 g, 394 mmol) are dissolved in 400 ml of glacial acetic acid and slowly i treated with iodine monochloride (13.5 ml, 264 mmol) at 0 °C. The reaction rnixture is then slowly warmed to room temperature and stirred for 15 hours. After addition of water (131), the formed precipitate is filtered off and washed with water. The filter cake is then dissolved in a minimal amount of tetrahydroturane (about 150 ml) and decolorized with IM aqueous sodium rhiosulfate. The product is piecipltated by the addition of water

(about 2.01), filtered off and dried at 60 °C for 12 hours. 423 g (89 %) white solid. MS: m/e= 364 (M+).
Example 399
(4-Memo:xy-benzothiazol-2-yl)-carbamic acid methyl ester
2-Arnmo-4-methoxyberrzothiazol (23.6 g, 131 mmol) and pyridine (12.6 ml, 157 mmol) in dichloromethane (230 ml) are slowly treated with methyl chloroformate (10.6 ml, 137 mmol) at 0 °C. After 10 minutes, further methyl chloroformate (1.0 ml, 13 ramol) and pyridine (1.0 ml, 12 mmol) are added. After 10 minutes, the mixture is poured into 200 ml 1M aqueous hydrochloric arid, the organic layer is separated, diluted with dichloromethane (250 ml) and washed with brine (50 ml). The organic phase is dried and the solvent evaporated in vacuo. 31.0 g (99.4 %) white solid. MS: m/e= 238 (M+H*).
Example 400
f4-Memoxv-7-phenyl-4?eiizoyhiazol-2-yl)-carbamic acid tert-batvi ester
To a suspension of 2-armno-4-memoxy-7-phenyi-benzothiazole (1.0 g, 3.9 mmol) in THF (50 ml) was added di(tert-butoxycarbonyl)-anhydride (BOC)20 and DMAP (47 mg, 0.04 mmol) and the mixture stirred for 1 h a r.L, followed by 3 h at 60 °C After cooling the solvent was evaporated and the residue chromatographed over SiOz (Merck 230-400 mesh) eluting with a gradient of cydohexane/EtOAc (10 % to 50 % EtOAc), after pooling the product fractons and evaporation of the solvents the title compound was obtained as a white foam (1.1 g, 79 % yield), MS: m/e=356 (M*).
Example 401
f4-Methoxy-benzothiazol-2-yl)~carbamif- acid tert-butyi ester
Using 2-amino-4-mefhoxy-benzothiazole the title compound was obtained as a white solid (60 % yield), MS: m/e=281.2 (M+H*).
Example 402
2-Amino-4-methoxy-7-phenyl-benzotfaLazoIe
The title compound was prepared from 3-ainmo-4-methoxy-biphenyi, according to the patent literature N~(Benzothiazol-2-yl)oxamic acid derivatives. W. Winter, M. Thiel, A.

Roesch and O. H. Wflhelms, German Patent, DE 2656468,1978. and is obtained as a white solid, MS: m/e=256 (M*), mp. 207-208 °C.
Example 403
4-Memoxy-7-phejioxy-benzotfaiazol-2-yl-amine
To a suspension of 2-memoxy-5-phenoxy-phenyi)-thiourea (8.25 g, 30 mmol) in CHO3 (70 ml) was added bromine (4.8 g, 30 mmol) in CHQ3 (10 ml) dropwise over 10 min. The mixture was then heated to reflux for 3 h, then cooled to r.t, the solvent was evaporated and the residue crystallised from MeOH/ether (1:4). The filter cake was then further washed with saturated aqueous NaHS03 solution /water (1:1), (100 ml), water (200 ml), IN NaOH (60 ml), then water (100 ml), and finally ether (100 ml). The solid material thus obtained was dried under vacuum (0.05 mmHg, 60 °C) to afford the tide compoud as a white solid (6.7 g, 82 % yield), MS: m/e=272.1 (M*).
Following the general method of example 403, the compounds of examples 404 to 409 were prepared
Example 404
?.-Amino-4-medioxy-benzothiazole-7-carboxYhc arid methyl ester
Using 4-methoxy-3-thioureido-benzoic acid methyl ester the title compound was obtained as a white solid (55 % yield), MS: m/e=239.2 (M+H4).
Example 405
7-Bromo-4-methoxy"benzothiazole-2-yl-aiTiinf
Using (5-bromo-2-methoxy-phenyl)-thiourea the title compound was obtained as a white solid (46 % yield), MS: m/e=258 (M*).
Example 406 7-tert-Butyl-4-methoxy-benzothiazole-7--vl-aTTiinp
Using (5-tert-butjd-2-metfaoxy-phenyl)-rhiourea the title compound was obtained as a white solid (79 % yield), MS: m/e= 238.1 (M*).

Example 407
7- Acetyjarmnn -4-methoxy-h«!"n74t4ia2oIe-2-vl-arninf
Using (5-acelyIamino-2-methoxy-phenyl)-thiourea me title compound was obtamed as a purple solid (49 % yield), MS: m/e=238.2 (M+fT.)
Example 408
4-methoxy-7-(" lH-tetrazoI-5-yI Vhen snthia7.pl-2-yj-amin4
Using 2-methoxy-5-(lH-tetrazol-5-yl)-phenyl]-thiourea die title compound was obtained as a tan solid (54 % yield), MS: m/e=248.2 (M*)
Example 409
f4-Methoxy-7-phenyi4?en2otHazol-2-yl)-methyl-arnine
Jsing (4-medioxy-biphenyl-3-yl)-thiourea the title compound was obrtained as a white ;olid (71 % yield), MS: m/e=270.1 (M+).
Example 410
5-Memoxy-7-phenyI-benzothiazoI-2-Yl-amin"e
(5-Methoxy-biphenyl-3-yl)-thiourea (109 mg, 0.42 mmol) in chloroform (2 ml) are treated with bromine (22 ul) and the mixture heated to 61 °C for 5 hours. After removal of the volatile components in vacuo, the product (93 g, 86 %) is isolated by flash chromatography (silica, eluent ethyl acetate/cyclohexane 2:1 to 5:1) as beige solid. The regiochemistry of the cychzation was checked by transfer-NOE measurements. MS: m/e= 256 (M+).
Example 411
?.- Ami n ft4,5-dimethoxvbari20thiazol
2-Ammo-4,5-o!imetlioxybanzothiazol is synthesized starting from 2,3-dimethoxyaniline (1.0 g, 6.5 mmol) in the same manner as described for 5-memoxy-7-phenyl-benzothiazol-2-yl-amine in 72 % total yield over three steps. MS: m/e= 210 (M*).

Example 412
6-Bromo4trifluoromemoxy-benzothiazol-2-yl-arnTnfi
4-Bromo-2-irifluoromethoxy)aruline (768 nig* 3 mmol) and potassium thiocyanate (875 mg, 9 mmol) are dissolved in acetic acid (5 ml) and at 0 °C, bromine (0.19 ml, 3.6 mmol) are slowly added. After stirring for 1 h, acetic acid (2 ml) are added and the mixture heated to 100 °C for 3 h. After cooling to room temperature, aqueous sodium hydroxide (10M, 25 ml) is added and the mixture extracted three times with ethyl acetate. The combined organic layers were wasged with brine, dried and the solvent removed in vacuo. Hash chromatography (silica, eluent ethyl acetate/cydohexane 1:4) and final recrystaHization from ethyl acetate/cydohexane affords the product as white solid. 170 mg (18 %). MS: m/e= 315 (M+rT).
Example 413
4-Memoxv-7-morpholm4-vl->w47r>r}iiazol-2-yl-amJne
(2-Methoxy-5-morpholin-4-yl-phenyl)-thioiarea (5.0 g, 19 mmol) in chloroform (130 ml) are treated with bromine (960 ul) and the mixture retluxed for 18 hours. After removal of the volatile components in vacuo, the product is recrystallized from THF (2.8 g, 57 %). MS: m/e= 266 (M*).
Example 414
7- Benzylpxy -4-memoxy-benzothiazole-2-yl-amine
Synthesized starting from (5-Benzvloxy-2-methoxy-phenyl)~thiourea in the same manner as described for 5-memoxy-7-phenyl-benzotbiazol-2-yl-amine in 82 % yield as a beige solid. Mp: 165 °C (dec).
Example 415 4-Trifluoromethoxy-benzotlua7ol-2~yl-ariune
6-Bromo4lrifiujDrometb,oxy~ben2otlu4ol-2-ylamine (157 rag, 0.50 mg), triethylamine (0.21 ml, 1.5 mmol) and palladium on carbon (10 %, 15 mg) are suspended in ethanol (12 ml) and hydrogenated at atmospheric pressure for 96 h. The catalyst was filtered off and the solution evaporated to dryness. The residue was dissolved in ethyl acetate, washed three times with water, dried and the solvent removed in vacuo. The product is obtained as brown solid (85 mg, 73%). MS: m/e= 235 (M+H*).

Example 416 -Amrno-4-methQxy-benzothia2ole-7-carbaldehvde
fsing (5-Fonnyi-2-methoxy-phenyI)-thiourea the title compound was syrithesised as escribed for 4-methoxy-7-phenoxy-benzotBia4I-2-yl-amine and obtained as a beige solid 70 % yield), MS: m/e=208.0 (M*).
Example 417
-Memoxy-7-morphoUn4Ymielhyl-berizotHa4
To a suspension of 2-amino-4-methoxy-ben20thiazole-7-carbaldehyde (440 mg, 2.1 nmol) in THF (100 ml) was added morpholine (276 mg, 3.2 mmol), acetic acid (190 mg, 5.2 mmol) followed by NaBH(OAc)3 (672 mg, 3.2 mmol). This mixture was stirred rigorously at 20 4C for 48 hours, after which time water (50 ml) and 5 % NaHC03 solution 450 ml) were added and the mixture agitated vigorously. After separating the organic and iqueous layers, the aqueous phase was extracted with EtOAc (50 ml) and the combined organic phase was washed with saturated Nad solution (100 ml) then dried with Na4SO*, filtered and evaporated. The solid residue was suspended in ether (20 ml) and filtered then the filter cake was washed with ether (10 ml), and dried under vacuum (O.05 mmHg, 50 °C) to afford the title compound as a yellow solid (430 mg, 73 % yield), MS: m/e=280.2
Example 418
2-Chloro-4-methoxy-7-phenvl-benzothiazole
To a suspension of 2-arnino-4~memoxy-7-paenyl-benzoliiiazole (5.1 g, 20 mmol) in ethylene glycol (75 ml) were added hydrazine monohydrate (4 g, 80 mmol) and hydrazine dihydrochloride (4.2 g, 40 mmol) and the suspension was heated for 18 h at 140 °C After cooling to r.L the suspension was filtered, then the filter cake was washed with water (200 ml) followed by ether (100 ml), and dried under vacuum (0.05 mmHg, 70 °C) to afford 2-hydrzmo-4-methosy-7-phenyl-ben2othiazole as a white solid (5.2 g, 96 % yield). The 2-hydjrzirio-4-memoxy-7-phenyl-ben2othiazole (4.5 g, 16.6 mmol) was then added in portions over 20 rain, to stirred neat thionyl chloride (12 ml, 165 mmol), the mixture was then heated to 50 °C for 2 h to complete the reaction. The reaction mixture was then cooled and poured on to ice/water (300 ml) and stirrd for 20 min. at 0-10 °C. The whole mixture was then filtered and the filter cake waas washed with water (100 ml). The filter mke wa? then dissulnulmCH4Q; (250 mi) and-washed wife wtttiatcdNgQaohrtwthThe

organic phase was dried with Na4C4 filtered and evaporaterd to aflfbed a red oil which was chromatographed over SiC>2 (Merck 230-400 mesh) eluting with CrtCb- The product fractions were pooled and evaporated to afford the title compound as a brown solid (4.24 g, 93 % yield), MS: m/e=275.0 (M*).
lit: Synth. Commun., 1992,2769-80.
Example 419
4-(Morpholine-4-sulfonyl)-benzoic acid
To a solution of 4-(chlorosulfonyi)-benzoic acid (05 g, 22 mmol) in THF (20 ml) was added morpholine (0.434 ml, 5 mmol) dropwise over 5 min, and this mixture stirred at r.t.for 1 h. Water (50 ml) was then addedand the mixture agitated, the phases were separated and the aqueous phase extracted with EtOAc (2x50 ml). The combined organic phases were washed with satd. aq. NaCI solution, dried, filtered and evaporated. The residue was chromatographed over S1O2 (Merck 230-400 mesh) during with a CHG3/Cacetone +10 % HCO2H) (9:1), the product fractions were pooled, evaporated and dried in vacuo (0.05 mmHg, 50 °C) to afford the title compound as a beige solid (270 mg, 20 % yield), MS: m/e=s271 (M*).
Following the general method of example 419, the compounds of examples 420 to 422 were
prepared
Example 420 4-Dipropylsulfamovl-benzoic acid
Using dipropyiamine the title compound was obtained as a beige solid, MS: m/e=285 (M*)-
Example 421 4-Ethylsulfamoyi-benzoic acid
Using ethyiamine the title compound was obtained as a white solid (85 % yield), MS: m/e=228.1 (M-H)Example 422
tylsuhami

Using diethyjamine me title compound was obtained as a white solid (44 % yield), MS: m/e=257 (M*).
Example 423
l-( 1,1 -Dioxo-tiuomorphohii-4-yIVethylamine
The tifle compound was prepared according to the following patent literature: W. R, Baker, S. A. Boyd, A. K. L Fung, H. H Stein, J. F. Denissen, C. W. Hutchins and S. H. Rosenberg, WO 9203429 (1992).
Example 424
MemyH4ffletfavl-pyridin-3-vlropitTiv1)-arninR
To a suspension of liAlHt in THF (120 ml) at 10 °C was added a solution of methyl-6-methyl nicotiiiate (12 g, 79 mmol) in THF (80 ml) dropwise with cooling over 45 win. After stirring 1.5 h at 20 °C, a mixture of THF/water (4:1) 60 ml was added to the reaction over 30 min. at 0 °C, NazSC>4 (50 g) was then added dircuy to the reaction mixture which was stirred vigorously, then filtered and the THF evaporated in vacuo. The residue was chromatographed over S1O2 (Merck 230-400 mesh) eluting with a gradient of CHidj/MeOH (97:3 to 9:1), affording a colourless oil (7.5 g, 77 % yield). This material was dissolved in CHQ3 (100 ml) and treated dropwise with thionyl chloride (17.2 ml, 237 mmol) stirred at 5 °C to 20 °C over 16 h. The solvents were then removed in vacuo and the residue partitioned between CH2C2 (100 ml) and aq. 5% NaHCC>3 (100 ml), the aqueous phase was further extracted with CH2CI2 (2x 50 ml) and the combined extracts washed with satd. aq, NaCI solution (1x50 ml), then dried and the solvent evaporated in vacuo. The resulting red oil was dissolved in EtOH (80 ml) cooled to 0 °C and treated with 33% memyiamine /EtOH (50 ml) dropwise over 1 h, then the mixture was stirred to 20 °C over 3 h. After evaporation of all the solvents the residue was partitioned between CH2Q2 and water (100 ml ea.), the aqueous phase was further extracted with CH2G2 (2x 100 ml), dried (Na2S04), filtered and the solvent evaporated in vacuo. The brown oily residue was then distilled under high vacuum (0.1 mm Hg, 68-70 °C) over a Vigreux column to afford the title compound as a pale yellow liquid (6.03 g, 75 % yield), MS: m/e= 136.1 (M*).
Lit/. Med. Chem., 1996,5053-63.
Following the general method of example 424, the compounds of examples 425 to 4266 were prepared

Example 425 Methyl-pyridin-2-yl-mfithyt-ainin e
Using 2-cHoromethyl-pyridine hydrochloride salt and 33 % methylamine/EtOH the title compound was obtained as a colourless liquid (0.1 mm Hg, 47-48 °C) (20 % yield), MS: m/e=93.1 (M-NHCH3).
Example 426
Methyl-pyridin-4-vlniethyl -amine-.
Using 4-chloromethyl-pyridine hydrochloride salt and 33 % methylamine/EtOH the title compound was obtained as a colourless liquid (0.1 mm Hg, 60-62 °C) (79 % yield), MS: m/e4I22.1 (M*).
Preparation of intermediates for examples 188 to 208
Example 427 2-Methoxy-5-phenoyy-plienyl)-thiourea
To a solution of 2-methoxy-5-phenoxy-aniline (9.9 g, 46 tnmol) in acetone (60 ml) was added benzoylisothiocyanate (9 g, 55 mmol) and the mixture heated to reiux (56 °C) for 4 h. After cooling to r.t., the solvent was evaporated and the oily orange residue was precipitated from ether (20 ml) under ultrasonnication, the solid was then washed on the filter with ether/ nHexane (1:3) (50 ml). The solid thus obtained was further dried under vacuum (0.05 mmHg, 50 °C) to afford the benzoylated thiourea as a beige solid (17.2 g, 99 %, yield). Fresh sodium metkoxide (14.5 g, 38 mmol) was men added to a suspension of the benzoylated thiourea (14.5 g, 38 mmol) in methanol (70 ml) and this mixture stirred for 1 h at r.t. Water was then added (210 ml) and the precipitated solid was collected, then washed on the filter with water (100 ml), followed by ether (100 ml), then dried under vacuum (0.05 mmHg, 50 *C) to afford the title compound as a white solid (8.5 g, 81 % yield), MS: m/e=274.1 (M*).
Following the general method of example 427 the compounds of examples 428 to 433 were prepared
Example 428 (5-tert-Butyl-2-methoxv-phenvl)-thiourea

Using 4-tert-buty!-2-methoxy-aniliQe the title compound was obtained as a white solid (79 % yield), MS: m/e=238.1 (M*).
Example 429
i"5-Acetviamino-2-methoxy-pheny])"thipurea
Using 3-an2ino-4-metho2face£anilide the title compoimd was obtained aS a grey solid (69 % yield), MS: m/e= 240.3 (M+H*).
Example 430
4-Methoxy-3-thioureido-benzoic acid methyl ester
Using 3-Amino-4-methoxy-benzoic acid methyl ester the title compound vras obtained as a tan solid (78 % yield), MS: m/e=240.0 (M+).
Example 431
f5-Bromo-2-methosy-phen4)-diiourea
Using 5-bromo-2-methoxy-aniline the title compound was obtained as a white solid (88 % yield), MS: m/e=260 (M*).
Example 432
2-methoxy-5-QH-tetrazol-5-yl)-phenyii-thiourea
Using 2-methoxy-5-(lH-tetrazol-5-yl)-anuine the tide compound was obtained as a tan solid (92 % yield), MS: m/e=250.1 (M+).
Exampl433
1 -f4-Metho:CT-biphen¥i-3-yl)-3-memYi-thiourea
Using 4-methoxy-biphenyi-3-ykmine and N-methyi-isothiocyanate the title compound was directly obtained as a white solid (96 % yield), MS: m/e=273.2 (M+rT).
Example434 (5-Methoxv-biphenyI-3-ylVuiioiirea
l-Benzoyl-3-(5-methosy-biphenyl-3-yl)-thiourea (183 mg, 0.51 mmol) in methanol (5 ml) are treated with sodium methoxide (5.4M in methanol, 0.14 ml) and the formed pxecipitsle is Altered aflL Washing with p4hann? yifiirii **>*• pnaduct (115 iflfc4 %J as, oi£r white powder. MS: m/e= 258 (M*).

Example 435
1 -Benzovi-3- (5-methoxy-biphenvl-3-yi Vthioorea
5-Methoxy-biphenyl-3-ylamine (129 mg, 0.65 mmol) are dissolved in acetone (5 ml) and slowly treated with a solution of benzoyl isothiocyanate (0.096 ml, 0.71 mmol) in acetone (2 ml). After stirring at ambient temperature for 18 h, the solvent is removed in vacuo and the residue crystallized from hexane. The product (203 mg, 86 %) is obtained as colorless crystalk Mp 149 °C.
Example 436
(2-Methoxv-5-morpho"in-4-yi-phenvl")-thiourea
1 -Benzoyi-3-(2-methoxy- 5- morpholin-4-yl-phenyl) -thiourea (8.0 g, 21 mmol), suspended in methanol (260 ml), are treated with 6 ml sodium methanolate (5.4M in methanol) and the mixture stirred until a white precipitate forms. The mixture is concentrated in vacuo, the crystals are isolated by filtration and washed with methanol and hexane (5.0 g 86 %). MS: m/e= 268(14).
Example 437
l-Benzoyl-3-f2-memoxy-5-morpholin-4-vl-phenylVthiouTea
To a solution of 2-methoxy-5-morphoIm-4-yI-phenyIamine (4.6 g, 22 mmol) in acetone (140 ml) is added a solution of benzoyl isithiocyanate (3.4 ml, 25 mmol) in acetone (80 ml) and the reaction mixture is stirred for further 30 min at ambient temperature. After removal of the volatile components in vacuo, the product is isolated by flash chromatography (silica, eluent ethyl acetate/n-hexane 1:4, then 1:2) as a yellow solid (8.0 g, 97 %). MS: m/e= 272 (M*).
Example 438 (5-BenzyJoxv-2-memoxy-phenvlV thiourea
Synthesized from 5-benzyloxy-2-methoxy-aniline as described for example 427 in 80 % overall yield. Obtained as white crystals. M.p. 130 °C (dec.).
Example 439 (5-Fomiy42-ipetiw)«v-4)bew4>-tiBottrea

To a solution of 2-(4-methoxy-3-nitro-phenyl)-[13]dioxolane (13 g, 57.7 mmol) in MeOH (400 ml) was added Adams catalyst-Pt(02) (700 mg) and the mixture stirred vigorously under an atmosphere of hydrogen at 20 °C until 41 of hydrogen had been taken up. The catalyst was then filtered off and and methanol evaporated and replaced with acetone (150 ml). Benzoyl isothiocyanate was then added dropwse (8.5 ml, 63.5 mmol) over 15 min at r.Land the mixture then heated to reflux for 1.5 h. After cooling the solvent was evaporated and the residue was chromatographed over SiCh (Merck 230-400 mesh) eluting with CH2Q2 affording a yellow oil (10 g). This oil was teken up in MeOH (150 ml) and sodium methoxide was added (3.7 g, 69 mmol) and the mixture stirred at 20 °C for 1 h. Following this the solvent was evaporated and the residue dissolved in THF (200 ml) and 2N HO (100 ml) was added and the mixture stirred for 30 min. EtQAc (200 ml) was then added and the aqueous phase separated and extracted with EtOAc/THF (1:1) (200 ml). The combined organic phases were washed with satd. aq. NaCl solution (2x 200 ml), dried, filtered and the solvent evaporated. The solid residue was suspended in ether (100 ml) and filtered off, washed with emer (50 ml) and drid under vacuum (0.05 mmHg, 50 °C) to afford the title compound as a yellow solid (4.7 g, 39 % yield). MS: m/e=210.1 (M*).
Example 440 2-(4-Mel3ioxy-3-nitro-phenviV 1131 dioxolane
To a solution of 4-methoxy-3-nito-ben2aldehyde (11.2 g, 61.8 mmol) in toluene (300 ml) was added ethylene glycol (5.2 ml, 92.7 mmol) and Amberlyst A15 resin acid catalyst (0.6 g). This mixture was stirred vigorously at reflux for 16 h. in a Dean-Stark apparatus. Upon cooling the Amberlyst resn was filtered off and the filtrate washed with satd. aq. Nad solution (3x150 ml), then dried with Na2SO*, filtered and evaporated to aflbrd the title compound as an orange oil (14 g, 100 % yield), MS: m/e=224.1 (M-H)Example 441 2-Meihoxv-5-f lH-tetrazol-5-vlVaDilmp
To a solution of 4-methoxy-3-nitro-benzonitrile (2.5 g> 1.4 mmol) in toluene (20 ml) was added sodium azide (1.3 g, 1.8 mmol) and triethylamine hydrochlride (1.5 g, 1.8 mmol), and this mixture stirred at 100 °C firo 48 h. Water was then added (200 ml) and the mixture ) agitated, the aqueous phase was further washed with water (2x30 ml). The organic phase was then adjusted to pH 2 and the solid which precipitated was filtered off and washed further with water (100 ml) then dried in vacuo (0-05 mmHg, 60 °C) to afford the crude tetrazole. This material was then directly dissolved in MeOH (80 ml), Pd/C (10%) (250

mg) was added and the mixture stirred under 1 atm of hydrogen at 20 °C for ca.1 h until the theoretical amount of hydrogen (ca. 880 ml) had been taken up. The catalyst was then filtered off and the solvent evaporated to afford the title compound as a white solid (2.2 g, 82 % yield), MS: m/e=191.1 (M*).
Lit Synthesis 1998, p910.
Example 442 1 -Iodo-3-methoxy-5-nitro-benzene
l-Iodo-3,5-dinitrobenzene (1.8 g, 6.1 mmol) are dissolved in methanol (12 ml) and treated with a solution of sodium methoxide in methanol (5.4M, 1.2 ml). The mixture is then stirred at 65°C for 52 h. After cooling to ambient temperature, water (50 ml) is added and the mixture extracted three times with ethyl acetate (50 ml). The combined organic layers are extracted with brine (100 ml), dried and evaporated to dryness. Hash chromatography (silica, eluent ethyi acetate/cydohexane 1:1) affords the product (1.7 g, 99%) as light yellow solid. MS: m/e= 279 (M*).
Example 443 S-Methoxy-biphepyl - Vyl-armTip
3-Methoxy-5-nitro-biphenyl (176 mg, 0.77 mmol) are hydrogenated in ethanol (5 ml) using palladium on carbon (20%, 17 mg) at atmospheric pressure for 2h, The caklyst is filtered off and the solvent removed in vacuo. Flash chromatography (silica, eluent ethyl acetate/cydohexane 1:1) affords the product (139 mg, 91 %) as a bown oil. MS: m/e= 199
(M+).
Example 444 2-Memoxv-5-morpholin-4-vl-phpny1amiTie
4-(4-Methoxy-3-nitro-phenyl)-morpholine (6 g) is hydrogenated in dichloromethane (100 ml) and methanol (600 ml) using palladium on carbon (10 %,600 mg) for 12 hours. The catalyst is removed by filtration and the solution evaporated in vacuo. Purification by flash chromatography (silica, eluent ethyl acetate/n-hexane 1:1, then ) affords the product as off-white solid (4.6 g, 88 %). MS: m/e= 209 (M+H+).

Example 445
4-f4-Methoxv-3-nitro-phenyD-morpholine
4-Bromo-2-nitroanisol (8.5 g, 36 mmol)> morpholine (3.8 ml, 44 mmol), potassium phosphate (11 g, 51 mmol), 2-biphenvI-dicyclohexyl phosphine (960 mg, 2.7 mmol) and palladium(n)acetate (411 mg, 1.8 mmol) are dissolved in dimethoxyethane (80 ml) and stirred at 80 °C for 96 hours. The mixture is then cooled to room temperature, diluted with ethyl acetate (50 ml) and filtrated through dicalite. Flash chromatography on. silica (eluent dichloromethane/methanol 99:1) affords the product as red solid (6.0 g, 69 %). MS: m/e= 238 (M+).
Example 446 3-Methoxy-5-nitro-biphenyl
l-Iodo-3-methoxy-5-nitro-benzene (279 mg, 1 mmol), phenyiboronic acid (146 mg, 1.2 mmol), potassium carbonate (2M, 1.0 ml) and tetrakis(triphenvlphosplnho)palladium(0) are dissolved in ethanol (0.5 ml) and toluene (10 ml) and the mixture heated to 90 °C for 24 h. The volatile components are removed in vacuo and the residue codistiUed twice with toluene. Flash chromatography (silica, eluent dttchloromethane/cyclohexane 1:2) affords the product (185 mg, 81 %) as light brown solid. MS: m/e= 229 (M1").
Example 447 5-Bromo-2-methox7-aniline
A solution of 4-bromo-2-ni£ro-anisole (7.7 g, 33.1 mmol), triethylamrae (4.6 ml, 33.1 mmol) and Raney Nickel catalyst (4 g) was vigorously stirred in ethanol (30Q ml) under an atmosphere of hydrogen for 1 h at 20 °C. After this time the theoretical amount of hydrogen had been absorbed (2.51), so the catalyst was filtered off and the solvent evaporated to afford the title compound as a light yellow solid (7 g, 104 % yield), MS: m/e= 201 (M*).
intermediates for the preparation of benzvlic amines
Example 448 4-Chloromethyl-N-f4-hydroxv-7-morpholm4yl-bei4omiazol-2-yl)-benzarniHf"
N-(4-Benzyloxy-7-morpholin4yl-ben20thiazol-2-yl)4chloromemyl-benzaniide (1.0 g, 2-Q mmol) were, dissolved uiCHaCla (10 ml) andtreated.at-78. °CwiIhtetrabutyi

ammonium iodide (0.95 g, 2.6 mmol) and a solution of boron trichloride in CH2U2 (.IM, 7.4 ml). After subsequent warming to 0° and stirring for additional 2 h, ice (2 g) and then water (10 ml) and methanol (2 ml) were added and the phases separated. The aqueous phases were extracted twice with CHjQj/MeOH, the combined organic layers "were dried with Na2S04 and evaporated to dryness. Recrystallization from CHjCfe/MeOH afforded the title compound as an off-white solid (18 %). MS: m/e= 403 ([M-H*]").
Example 449
4-fl-Bromo-emvl)-N-(4-me&o4-7-morpholm4yl-te
Following the general method of example 1 the title compound was obtained as a yellow
solid (63 %). MS: m/e= 478 (M+rT).
Example 450
3-ChloromethvI-N"(4-memoxy-7-morphoh44yl-benzothiazol-2-ylVben?.arniflp Following the general method of example 1 the title compound was obtained as a light yellow solid (59 %). MS: m/e= 418 (M+H*).
Example 451
4-Chloromemyi-3-fiuoro-N-(4-methoxy-7-morpholm4vI-benzotrn4ol-2-4Vbenzamide Following the general method of example 1 the title compound was obtained as a light brown solid (99 %). US: m/e= 436 (M+H*).
Example 452
4-Chioro-3-chIoromemyi-N-(4-methoxy-7-morpholm4
Following the general method of example 1 the title compound was obtained only in 75%
purity (68 %) and used in the subsequent steps without further purification. MS: m/e= 452
(M+FT).
Example 453
4-ff2-Methoxy-ethYl)-methvl-sulfamoyn-ben2oicacid
4-Chioro-suIfonyl-benzoic acid (100 mg, 0.45 mmol) were dissolved in (2-methoxy-ethyI)-methyl-amine (1.0 g, 11.2 mmol) and heated to 50 °C for 18 h. Removal of the volatile components in vacuo and flash chromatography (silica, ement C4CyMeOH/FkO/AcOH 90:10:1:1) afforded the product as white solid (65 %). MS: m/e= 272 ([M-H]")-
ftniwmerfTflteg fui trie pieyiaiaftomTrl)ffii/yTTi_aniinesfer54-OBg?

Example 454
4-Benzvloxv-7-moiphou44)d-benzolhia2ol-2-yi-amine
Using 2-benzyloxy-5-morpholm-4-yl-phenyl)-tbiourea following the general method of
example 403 the title compound was obtained as off-white solid (69 %). MS: m/e= 342
(M+H*).
Example 455
N-f4-Benz4oxv-7-morpholin-4-)d-benzoimazol-24-4-cMorometfa4-bpn7.arTiiHf; Following the general method of example 1 the title compound was obtained as a pale yellow solid (81 %). MS: m/e= 494 (M+H+).
intermediates for the preparation of benzync amines for changed 7-position:
Example 456
4-Memoxv-7-thiomorpholm-4-yl-benzotma2ol-2-yl-amuie
Using 2-methoxy-5-thiomorpholin-4-yl-phenyi)-tbiourea following the general method of
example 403 the title compound was obtained as light brown solid (31 %). MS: m/e= 282
(M+H*).
Example 457
f4-Methoxv-7-l"2-methvi-pyridm-4Yl)-hf"Ti7nfhia7ol-2-Yli-carbarm"c add methvl ester Using the general procedure B the title compound was prepared from 4-methoxy-7-morpholin-4-)d-benzothiazol-2-4-aniine and 2-meth}4-4-rrimetbylstannanyl-pyridine as a white solid (8%). MS: m/e= 329 (M*).
Example 458
4-Memo4-7-(2-methv1-pyridm4-ylVbenzothiazo]-2-4-amine
[4-Memoxy-7-(2-methyl-pyridm4yl)-benzotmazol-2-yl]-caibarmc add methyl ester (100 mg, 0.24 mmol) were dissolved in ethyleneglycol (3.0 ml) and treated with potassium hydroxide (528 mg, 1.1 mmol) and heated to 100 °C for 6.5 h. The reaction mixture was cooled to room temperature, diluted with water, neutralized with IN HQ and extracted four times with ethyl acetate. The organic layers were combined and washed with water and saturated aqueous Nad. The organic phases were then dried and the solvent removed in vacuo. The product was obtained as a light brown solid (83 %). MS: m/e= 272 (M+H1").

wherein
R1 is hydrogen, Q-s-alkyl, Ci-6-aIkoxy, benzyloxy, cydoalkyioxy, halogen, hydroxy or trifluoromethyloxy;
R3 is hydrogen, halogen, (Ve-aJkyJ or Ci. R4 is hydrogen, C^-alkyi, C2-6-aUcenyl, halogen, -C(O)- Ci. R" is
(a) phenyl, substituted by halogen-Q_e-a]kyl, O(0)H or by the
following groups
-fCH2)n-C(0)-N(Rs)-(CH2>„ C^-alkoxy,
-CCH3)nO-halogen- C^-alky],
-(CH^O-fC^^O-Cr^kyl,
-S(0)2-N(R!)-(CHAO- Ci-6-alkyl,
-(CH2)nOR3, with the exception of OCHjandOH,
KCH2)nN(R5KCH2)0-Cl.(5-alkoxy,
-(CH^NfCCH^- C^-alkoxy]z,
-(CH2)nNfS(0)2CH3]2,
"(CH2)nN[R5J[SCO)2CH3J,

-(CH2)nN(R> Cz-e-atayl,
-{CH2)nN{R5)-(CH2)0-cycIoaIkjrl,
-(CH2)nN(R5)-C(0)0- d-s-alkyl,
-(CH^NC^MCHzk-S- Q.fi-alfcyl,
-(CH2)aN(R5)-S(0)2CH5
-(CH2)aN(Rs)-(CH2)D-phenyl,
-(CH2)»N(Hs)-(CH2)oOH,
-{CHi)nN{R3)-(CH2)oCH(OH)-CF3!
-(CH2)nN(R5)-(CH2)0-CF3>
-(CH2)DNCRs)-CCH:)0-O-CH(OH)-CsH3(OCH3)2,
-(CHaJnNCR^-CCH^o-O-aO-QHaCOCHa)!,
-N(R5)-C(0)-morpholin>
- N(R5)-C(0)-N(R5)-phenyl, substituted by Ci^alkcacy,
-SCO 7-morpholin,
or is phenyl, which is substituted by -(CR5R6)D-five to seven membered aromatic Or
non aromatic heterocyde, and wherein the heterocyde may further substituted by hydroxy,
-N(R5)(R6)orCj^-aIikyl;
X is 0 or S;
R5, R6are independently from each other hydrogen or Ci^-alkyl,
R7 is d^alkyl, Cj^-alkoxy, -C(O)- Cus-alkyl, -C(0)Q-benzyI, -C(0)0- Ci-s-alkyl, - (CH2)nNR5R,s, pyridinyl, optionally substituted by Ci-s-alkyl, or is -CH2N(R5)-C(0)0-C1.s-aikyl, -NH-C(phenyI)3, pyrmlidinyl, piperidinyl, morpholinyl or piperazinyl, optionally substituted by Cj-s-alkyl;
n is 0,1,2,3 or 4;
m isOorl;
o is 0,1, 2, 3 or 4;
and their pharmaceutically acceptable salts,

Some minor subgroups of compounds of the present formula I are known compounds and have been described, for example in EP 427 963, US 5,099,021, EP 295 656 or DE19 53149. These compounds possess microbicide activity or may be used for lowering the blood glucose level Furthermore, WO 00/18767 describes 2-piperazino alkylamino benzoazole, having an affinity to the dopamine subtype specific Bgands and are therefore useful in the treatment of diseases, related to this receptor. The compounds of WO 00/18767 are not encompassed from the scope of the present invention.
It has surprisingly been found that the compounds of general formula. I are adenosine receptor ligands.
Adenosine modulates a wide range of physiological functions by interacting with specific cell surface receptors. The potential of adenosine receptors as drug targets was first reviewed in 1982. Adenosine is related both structurally and metabolically to die bioactive nucleotides adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and cyclic adenosine monophosphate (cAMP); to the biochemical methylating agent S-adenosyi-L-methione (SAM); and structurally to the coenzymes NAD, FAD and coenzym A; and to RNA. Together adenosine and these related compounds are important in the regulation of many aspects of cellular metabolism and in the modulation of different central nervous system activities.
The receptores for adenosine have been classified as Ai, A2A> A2B and A3 receptors, belonging to the family of G protein-coupled receptors. Activation of adenosine receptors by adenosine initiates signal transduction mechanism. These mechanisms are dependent on the receptor associated G protein. Each of the adenosine receptor subtyps has been classically characterised by the adenylate cyclase effector system, which utilises cAMP as a second messenger. The Ai and A3 receptors, coupled with Gj proteins inhibit adenylate cyclase, leading to a decrease in cellular cAMP levels, while A2A and AJB receptors couple to Gs proteins and activate adenylate cyclase, leading to an increase in cellular cAMP levels. It is known that the Aj receptor system include the activation of phospholipase C and modulation of both potassium and calcium ion channels. The A3 subtype, in addition to its association with adenylate cyclase, also stimulates phospholipase C and so Activates calcium ion channels.
The Aj receptor (326-328 amino acids) was cloned from various species (canine, human* iai* dog, ducl^bcivuie* guinear^rig) witiL9G^5& sequence identify amonftthe mammalian species. The AJA receptor (409-412 amino acids) was cloned from canine, rat,

human, guinea pig and mouse. The A^ receptor (332 amino acids) was cloned from human and mouse with 45% homology of human A2B with human Ai and A2A receptors. The A3 receptor (317-320 amino acids) was cloned from human, rat, dog, rabbit and sheep.
The Ai and A2A receptor subtypes are proposed to play complementary roles in adenosine"s regulation of the energy supply. Adenosine, which is a metabolic product of ATP, diffuses from the cell and acts locally to activate adenosine receptors to decrease the oxygen demand (Ai) or increase the oxygen supply (A2A) and so reinstate the balance of energy supply, demand within the tissue. The actions of both subtyps is to increase the amount of available oxygen to tissue and to protect cells against damage caused by a short term imbalance of oxygen. One of the important functions of endogenous adenosine is preventing damage during traumas such as hypoxia, ischaemia, hypotension and seizure activity.
Furthermore, it is known that the binding of the adenosine receptor agonist to mast cells expressing the rat A3 receptor resulted in increased inositol triphosphate and intracellular calcium concentrations, which potentiated antigen induced secretion of inflammatory mediators. Therefore, the A3 receptor plays a role in mediating asthmatic attacks and other allergic responses.
Adenosine is also a neuromodulator, possessing global importance in the modulation of molecular mechanisms underlying many aspects of physiological brain function by mediating central inhibitory effects. An increase in neurotransmitter release follows traumas such as hypoxia, ischaemia and seizures. These neurotransmitters are ultimately responsible for neural degeneration and neural death, which causes brain damage or death of the individual. The adenosine Ai agonists which mimic the central inhibitory effects of adenosine may therefore be useful as neuroprotective agents. Adenosine has been proposed as an endogenous anticonvulsant agent, inhibiting ghitamate release from excitory neurons and inhibiting neuronal firing. Adenosine agonists therefore may be used as antiepHeptic agents. Adenosine antagonists stimulate the activity of the CNS and have proven to be effective as cognition enhancers. Selective Aa,- antagonists have therapeutic potential in the treatment of various forms of dementia, for example in Alzheimer"s disease and are useful as neuroprotective agents. Adenosine A^- receptor antagonists inhibit the release of dopamine from central synaptic terminals and stimulate locomotor activity and consequently improve Parkinsonian symptoms. The central activities of adenosine are also implicated in the molecular mechanism underlying sedation, hypnosis, schizophrenia, anxiety, pain, respiration, depression and substance abuse. Drugs acting at adenosine receptors therefore have therapeutic potential as sedatives, muscle relaxants, antipsychotics, anxiolytics, analgesics, respiratory stimulants and antidepressants, and they may be used in the treatment of ADHD (attention deficit hyper-activity disorder).

An important role for adenosine in the cardiovascular system is as a cardioprotective agent Levels of endogenous adenosine increase in response to ischaemia and hypoxia, and protect cardiac tissue during and after trauma (preconditioning). Adenosine agonists thus have potential as cardioprotective agents.
Adenosine modulates many aspects of renal function, including renin release, glomerular filtration rate and renal blood flow. Compounds, which antagonise the renal affects of adenosine, have potential as renal protective agents. Furthermore, adenosine A3 and/or A2B antagonists may be useful in the treatment of asthma and other allergic responsesor and in the rxeament of diabetes mellitus and obesity.
Numerous documents describe the current knowledge on adenosine receptors, for example the following publications:
Bioorganic & Medicinal Chemistry, 6, (1998), 619-641,
Bioorganic & Medicinal Chemistry, 6, (1998), 707-719,
J. Med. Chem., (1998), 41,2835-2845,
J. Med. Chem., (1998), 41,3186-3201,
J. Med. Chem., (1998), 41,2126-2133,
J. Med. Chem., (1999), 42, 706-721,
J. Med. Chem., (1996), 39,1164-1171,
Arch. Pharm. Med. Chem., 332,39-41, (1999).
Objects of the present invention is the use of compounds of formula I and their pharmaceutically acceptable salts for the manufacture of medicaments for the treatment of diseases, related to the adenosine A2 receptor, novel compounds of formula I-A per se, their manufacture, medicaments based on a compound in accordance with the invention and their production as well as die use of compounds of formula I in the control or prevention of illnesses based on the modulation of the adenosine system, such as Alzheimer"s disease, Parkinson"s disease, neuroprotection, schizophrenia, anxiety, pain, respiration deficits, depression, asthma, allergic responses, hypoxia, ischaemia, seizure and substance abuse. Furthermore, compounds of the present invention may be useful as sedatives, muscle relaxants, antipsychotics, antiepileptics, anticonvulsants and cardiaprotective agents. The most preferred indications in accordance with the present
jnwntjf>n ar** *hn»T milifit Kacg nn the- A^ rtf Apfnr antstgcmicrir a^ti^ty a^ ^

lisorders of the central nervous system, for example the treatment or prevention of certain lepressive disorders, neuroprotection and Parkinson"s disease as well as ADHD and liabetes mellitus.
The present invention relates also to novel compounds of the general formula

wherein
R.1 is hydrogen, lower alkyl, lower alkoxy, benzyloxy, cydoalkyloxy, halogen, hydroxy or trifiuoromethyloxy;
R2, R3 are independently from each other hydrogen, halogen, lower alkyl or lower alkyloxy;
R4 is hydrogen, lower alkyl, lower aDcenyl, halogen, -C(0)-lower alkyk
-C(0)-halogen-lower alkyl, -CH(OH)-halogen-lower alkyl, -C(0)0-lower aDcyl,
-NHC(0)-lower alkyl, -(CH2)n-OH,
or is phenyl, which is optionally attached to the benzo group via the linker
~(0)m-(CH2)a- and is optionally substituted by N(R5)(R6), halogen or nitro,
or is 2,3-dihydro-lH-indolyl, azepan-1-yl, [l,4]oxazepan-4-yl, or is
a five or six membered aromatic or non aromatic heterocyde, which may be
attached to the benzo group via the linker -(0)m-(CH2)„ or -N=C(CH3)-
and is optionally substituted by one or two group(s) R7, wherein R7 is defined below;
R" is
(a) phenyl, optionally substituted by halogen-lower alkyl, -C(0)H or by the
following groups
-(CH2)n-C(0)-N(R5)-(CH2)nlower alkoxy,
-(CH2)nO-halogen-lower alkyl,
-(CH2)nO-(CH2)n+iO-lower aDcyl,
-S(O)2-N(R5)-(CH2)r0-Iower aDcyl,
-(CH2)D0RS,
-CCH2)i.N(R5)-(CH2)0-lower alkoxy,
-(CH2)nN[(CH2)0-lower aDcoxy]2,
-(CH2)nN[S(0)2GH3]2,
-CCH2)nK[R5jrsCO)2CH3],

-(CH2)nN(Rs)-lower alkenyl,
-(CH2)nN(R5)-(CH2)o-cycIoaIkyl,
-(CH2)nN(R5)-C(0)0-lower alkyi,
-(CH^-S-fCHbVNfR^R6),
-(CH2)nN(R5)-(CH2)0-S-lower alkyi,
-(CH2)nN(R5)-S(0)2CH3
-(CH2)amR5)-(CH2)0~phenji,
-(CH2)nN(R5)-(CH2)oOH,
-(CH2)nN(R5)-(CH2)0CH(OH)-CF3j
-CCH2)nN(R5)-(CH2)0-CF3,
-(CH2)DN(R5)-(CH2)O-0-CH(0H)-C6H3(0CH3)2J
-CCH2)nN(R5)-(CH2)o-0-C(0)-QH3(OCH3)2j
-N(R5)-C(0)-morpholin,
-N(R5)-C(0)-N(R5)-phenyi, substituted by alkoxy,
-S(0)2-morpholin,
or is phenyl, which is optionally substituted by
-(CR^Vfiveto seven membered aromatic or non aromatic heterocycle, and
wherein the heterocycle may further substituted by hydroxy, -N(R5)(R6) or lower
alkyi, or by -(CH2)nN{R5){CH2)0-nve or six membered aromatic or non aromatic
heterocycle and wherein the heterocycle may further substituted by hydroxy,
-N(R5)(R6) or lower alkyi,
or is -N(R5)-phenyl, which is optionally substituted by lower alkoxy, or
is
b) -{CH2)n-five or six membered aromatic or non aromatic heterocycle, with the exception of the the piperazinyi group in case if n=0, which rings may be optionally substituted by
2-oxo-pyrrolidin, piperidinyl, phenyl, -(CH2)nOH, halogen, CF3, =0, lower alkyi, cydoalkyi, -(CH2)n-0-lower alkyi, -(CH2)„NH2, -(CH2)nCN, -C(O)0-lower alkyi, -CH2-0-S(0)2CH3> -C(0)-lower alkyi, -C(0)-(CH2)c-lower alkoxy, -CHj-NfR^QHiF, -CH2-N(R6)C(0)O-lower alkyi,
-N(R6)-C(O)-N(R5)-(CH2)n-0-lower alkyi, -orby tetrahydrofuran, Substituted by 4-Q-phenyl, orbypipera2m-l-yl,morpholmyl,thiomorphoIinyI, thiomorpholin- 1-oxo, pyrroUdin-1-yl or by piperidin-1-yl or is benzopiperidin-1-yi or benzothien-2-yi, or

c) -N(R5)(CH2)n+i-phenyl, optionally substituted by lower alkoxy,
-0(CH2)n-phenyl, or
-N(R5)C(0)-phenyi, or
is
d) -N(R5)(CH2)n-5-or 6 membered aromatic or non aromatic heterocycle,
optionally substituted by lower alkyi, -(CH2)n-5-or 6 membered aromatic or non
aromatic heterocycle
oris
e) -0-(CH2)a-lower alkoxy, lower alkyl-iower alkoxy, -NtR^CH^BNfRW),
-(CH2)nOH, -(HC=CH)nC(0)0-Iower alkyi, octahydro-quinoline,
3,4-dihydro-lH-isoquinoline, 2^-ben2o-l,4-dioxa-8-a2a-spiro[4>5]decane or
1,4-dioxa-8-aza^spiro [4,5] decane.
X is O, S or two hydrogen atoms;
R5, R6 are independently from each other hydrogen or lower alkyi,
R7 is lower alkyi, lower alkoxy, -C(0)-lower alkyi, -C(O)0-benzyl, -C(0)0-lower alkyl, -(CHjJnNR^6, pyridinyl, optionally substituted by lower alkyl, or is -CH2N(R5)-C(0)0-lower alkyl, -NH-C(phenyi)3, pyrrolidinyl, piperidinyl, morpholinyi, piperazinyl, optionally substituted by lower alkyl;
n is 0,1,2,3 or 4;
m is 0 or 1;
o isO, 1,2,3 or 4;
and to their pharmaceutically acceptable salts for the manufacture of medicaments for the treatment of diseases related to the adenosine receptor.
As used herein, the term "lower alkyl" denotes a saturated straight- or branched-chain alkyl group containing from 1 to 6 carbon atoms, for example, methyl, ethyl, propyl, isopropyl, n-butyl, i-butyl, 2-butyl, t-butyl and the like. Preferred lower alkyl groups are groups with 1-4 carbon atoms.
As used herein, the tqxm "lower alkenyT denotes a nn.^tnrat^ straight- or branched-chain alkyl group containing from 2 to 6 carbon atoms, for example, ethylerj, propyien,

isopropylen, n-butyien, i-butylen, 2-butylen, t-butylen and the like. Preferred lower alkyl groups are groups with 2-4 carbon atoms.
The term "cycloalkyl" denotes a saturated carbocydic group, containing 3-6 carbon atoms.
The term "halogen" denotes chlorine, iodine, fluorine and bromine.
The term "lower alkoxy" denotes a group wherein the alkyl residues is as defined above, and which is attached via an oxygen atom.
The term "five or six membered aromatic or non aromatic heterocycle" denotes the following group: aromatic heterocyclic groups are, for example pyrrol-1-yl, tetrazolyl, imidazol-1 or 2-yl, pyrazoU-yl, pyridin-1,2,3 or 4-yl, pyrazinyl, pyrimidinyl, pyridazinyi, isothiazolyi, isoxazolyl, thiazolyl, thienyl or furyl; Non aromatic heterocyclic groups are, for example, pyrrolidinyi, imidazolidinyl, pyrazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyi, ttaomorpholin-l,l-dioxo or thiomorpholin-l-oxo.
The term "phannaceua"cally acceptable acid addition salts" embraces salts with inorganic and organic acids, such as hydrochloric acid, nitric acid, sulfuric acid, phosphoric acid, citric acid, formic acid, fumaric acid, maleic acid, acetic acid, succinic acid, tartaric acid, methane-sulfonic acid, p-toluenesulfonic acid and the like.
Preferred compounds of formula I are those, wherein R1 is methoxy, X is oxygen and R2/R3 are hydrogen.
Exemplary preferred are compounds of formula I for the above mentioned use, wherein R
is an unsubstituted or substituted five or six membered aromatic heterocycle, for example
the following compounds:
N-(4-methoxy-7-morpholm-4-yl-benzothiazol-2-yl)-2^
5-methvl-tbiophene-2-carboxylic acid (4-methoxy-7-phenyl-ben2omiazol-2-yI)-amideJ
5-methyl-furan-2-carboxylic acid (4-memoxy-7-phenyl-ben2ofhiazol-2-yl)-amide)
N-(4-memoxy-7-phenyl-benzotlnizol-2-yl)-isomcotinamide,
5-methyi-thiophene-2-carboxyiic acid (4-methoxy-7-pyridin-4-yl-benzomia2ol-2-yi)-
amide,
5-memyl-thiophene-2-carboxylic acid (4-memoxy-7-pyridm-3-yl-benzothiazol-2-yl)-
amide,
5-methyl-thiophene-2-carboxylic acid [4-methoxy-7-(2-methyl-pyridin-4-yl)-
benzothia2ol-2-yl] -amide,
^mrihyA^kif«-ith*«^-3^a»twgylif- VYJ [7-(^-a*"»Ty>-ph***yi) \ mfthrtigy h*f»i«vt"hiaTf\l-?.

yi]-amide,
N-(4-methoxy-7-l^ophen-2-)d-benzotiua2ol-2-yl)-2-methyl-isoiucotinamide>
N- [4-methoxy- 7-(2-pyridin-2-j4-t]iiazol-4-)d)-beiizothia2ol-2-yi]-2-meth)4-
isonicotinamide,
N-[4-inethoxy-7-(2-pyiToiidin-I -yi-tbiazol-4-yi)-benzothiazo]-2-yl] -2 -methyl-
isonicotinamide,
N-{4-methoxy- 7- [2-(4-methyI-piperaziri-1 -yi)-thiazol-4-y] J-benzotiia2oJ-2-yi}-2-metbyi-isonicotinamide and
N-[4-metiioxy-7-(5-metb)i-tHopb£n-2-^)-benzotbiazol-2-yI]-2-me&^-isordcotin
276
Further preferred compounds of formula I for the above mentioned use are compounds, wherein R is an unsubstituted or substituted five or six membered non aromatic heterocyde, for example the following compounds:
morphoIine-4--carboxyUc add (4-memoxy-7-phenyl-benzotbiazol-2-yl)-amide,
thiomorpholine-4-carboxylic add (4-memoxy-7-phenvl-ben2»thiazol-2-yl)-amide,
1-oxo-ll 4-thiomorpholine-4-carboxyhc add (4-methoxy-7-phenyl-benzothiazoI-2-yl)-
amide,
morpholine-4-carboxyHc add {4-memoxy-7-[2-(6-methyl-pyridm-3-7l)-thiazol-4-yi]-
benzothia2ol-2-yl}-aiiiide>
morphoIine-4-carboxyhc add [4-methoxy-7-(2-p)^dm-2-yl-diiazol-4-yl)-benzothiazol-2-
yl]-amide,
morpholine-4-carboxyhc add {4-methoxy-7-[2-(4-metiiyI-prpera2m-l-yl)-thiazol-4-yl]-
benzothiazol-2-yi}-amide,
morpholine-4-carboxyIic add [4-methoxy-7-C2-piperidm-l-yl-thiazol^yl)-berizothia2ol-
2-yl} -amide,
morpholine-4-carboxyiic add [4-methoxy-7-(5-methyi-tbiophen-2-yl)-benzothiazol-2-
yl]-amide,
4-(4-methco^-7-morphoIm-4-yl-beiizothia2»l-2-^
acid tert-butyl ester,
l-acetyl-piperidme-4-carboxylic add (4-methoxy-7-morpholm-4-yl-benzotbiazol-2-yl)--
amide,
4-oxo-piperidine-l-carboxykc acid (4-methoxy-7-morpb.olin-4-yl-benzouiiazol-2-yl)-
amideand
l-oxo-l>.4-thiomorpholine-4-carboxyuc add (4-memoxy-7-piperidin-l-yl-benzothiazol-• 2-yl>-aimde.

Preferred are further compounds, wherein R is methoxy, for example the following
compounds:
rac-[7-(2-bromo-l-hydroxy-ethyI)-4-memoxy-ben2ouiiazoI-2-yIJ-caTbaniic acid methyl
ester,
{4-metho:xy-7-[2-(6-mefhyl-pyria^-3-yl)-thia^
methyl ester,
[4-methoxy-7-(2-pyridm-2-yl-thiazoM-yl)-b^
[4-methoxy-7-(2-piperidm-l-yl-tm"azol^-yl)-benzothiazol-2-yl]-carbamk acid methyl
ester and
{4-methoxy-7- [2-(4-methyl-piperazin- l-yl)-diiazol-4-yl] -ben20thiazol-2-yl}-carbamic
acid methyl ester.
Preferred compounds of formula I for the above mentioned use are those, wherein R is
phenyl, optionally substituted by halogen, CF3, -CH2OH, -CH2NHCH2CH2OCH3> -CH2NHCH2CH2OH, -CH2NHCH2-pyridinyl> -CH2NH2, -CH2NHCH2CH2SCH3j -CH2N(CH3)CH2CH2SCH3,-CH2N(CH3)CH2CH2OCH3,
-CH3N(CH2 CH3)CH2CH2OCH3, -CH2NHCH3, -CH2SCH2CH2N(CH3)2, -Cf^OCHs, -CH2OCH2CH20CH3 or -CH2N(CH3)C(0)OCH3, for example the following compounds: 4-hydroxymetiiyl-N-C4-memoxy-7-phenyl-benzotHa2oI-2-yI)-benzarnide, 4-fluoro-N-(4-methoxy-7-phenyl-benzothiazol-2-yi)-ben2amides 2-{4-fluoro-benzoylanmio)-4-methoxy-benzotfuazole-7-carboxylic add methyl ester, 4- [ (2-memoxy-^thylarnmo)-methyl] -N-(4-methoxy-7-phenyl-benzothiazol-2-yl)-benzamide,
4-[(2-hydroxy-emylammo)-methyl]~N-(4-methoxy-7-phenyl-benzotfaiazoI-2--yl)-benzamide,
N-(4-melho:xy-7-phenyl-benzothiazol-2-yl)^{[(p benzamide,
N-(4-methoxy-7-pherryl-benzotluarol-2-yl)^{[te benzamide,
4-arm^ome^yl-N-C4-methoxy-7-phenyI-benz»thiazoI-2-yiJ-berizamide, N-(4-metiioxy-7-phenyl-benzothiazol-2-yl) -4- [(2-memylsul£myl-ethylamrno)-metbyl] -benzamide,
4-{^2-memoxy-^thyl)-memyl-anrmo]-metnyl}-N-(4-methoxy-7-morphoh^ benzothiazol-2-yl)-benzamide,
N- [7-(2-arnino-thiazol-4--yl) -4-metrioxy-benzodiiazol-2-yl]-4-fluoro-ben2amide, 4-fluoro-N-{4-methoxy-7- [2-(6^memyl-pyridin-3-yl)-thiazol-4-yl] -benzothiazol-2-yl}-

benzamide,
4-fiuoro-N-(4-methoxy-7-tbiophen-2-yi-benzothiazol-2-yi)-ben2aiiiide,
4-fluoro-N-{4-methoxy-7- [2-(4-methyl-piperazin-l -yO-thiazol-4-yl] -benzothiazol-2-yI}-
benzamide,
4-{[(2-methox7-etii^)-metii)d-amino]-meth7l}-N-{4-methoxj"-7-[2-(6-mefli^-pyridin-3-
yi)-thiazol-4-^] -benzotbiazol-2-5d}-benzamide,
4-{[(2-Methory-^yl)-methyl-ainino]-met^
benzothiazol-2-ji)-benzamide>
4-{[(2-methoxy"-ediyi)-metiiyI-anmo]-meth)^}-N-[4-methoxy^7-(2-pyridin-2-yi-diiazoI-
4-yl)-benzothiazol-2-yl]-benzamide,
N-(4-me^oxy,-7-morpholin^yi-benzodiiazol-2-)i)^ti^uorometh^-benzamideJ
4-fiuoro-N-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-^)-benzainide)
N-(4-metiioxy--7-morphoKn-4-yl-benzothiazoI-2-yI)-benzamide,
4-cMoro-3-{[ethyl-(2-metho:^-ediyl)-amino]-met^^
benzothiazoI-2-yI)-benzamide,
N-(4-methoxy-7-morphoIin-4-yl-beiizotMazol-2-yl)-3-me^
4-cMoro-N-(4-methoxy-7-morphoIin^yi-benzothiazol-2^
benzamide,
4-cMoro-3-{[(2-methoxy-ethyl)-methyl-aniino]-me^^
yl-ben£odiiazol-2-yl)-ben2amideJ
4-cUoro-3-[C2-me&oxy^-ethyiamino)-methyl]-N-(4^methoxy;-7-inorphoIia-4-yl--
benzothiazol-2-yl)-benzamide,
3-[(2-methoxy-ethylamino)-methyl]-N-(4-metto
yl)-benzamide,
3-i[(2-methoxy-ethyI)-meth)d-amiiio]-nK^yl}-N-(4-methoxy-7-moi7holin-4-yi-
benzotbiazol-2-yl}-beiizaEQide,
4-[(2-etho:^-ethylamino)-methyl]-N-(4-me&^^
ben/amide,
N-(4-methoxy-7-morpholin^yl-benzothiazol-2-yl)^m
4^2-dimethylamino-etbykul£mylmet^^
2-yl)-benzaniide>
4-{[(2-ethoxy-etiayl)-etbyl-ammo]-methyl}-N-(4-methoxy-7-morpholin^yl-
benzothiazol-2-yl)-benzamideJ
4-{ [(2-ethoxy-etiiyl)-methyI-amiiio] -methyl}-N-(4-nietb.oxy-7-morphdiii-4-yl-
ben201iiazol-2-yl)-benzainideJ
4-(?-methoxy-ethoxyrpetby1)-N-(4-metboyy^
benzamid

4-methoxymethyI-N-(4-methoxy-7-morphoIin^yU^ N-(4-methoxy-7-tiiiomorpholin-^>d-benzothiazol-2-yl)-benzaimdeand [4-(4-metiioxy-7-moipholm-4-yl-bermilhiazol-2-^ acid methyl ester.
Further preferred compounds of formula I for the above mentioned use are those, wherein R is phenyl, substituted by a optionally substituted -(CH2)n-five to seven membered aromatic or non aromatic heterocyde, for example the following compounds:
4-irmdazoI-l-yI-merhyl-N-(4-merhoxy-7-ph^
4-(4-Hydroxy-piperidm-l-yl-methyl)-N-(4-m
benzamide,
4-[l,4]diaKpan-l-yl-methyi-N-(4-methoxy-7-
4- (3 (S)-dimethylammo-pynrolidin- l-yl-methyl)-N-(4rmet]ioxy-7-phenyl-benzo1hiazol-2-
yl)-benzamide,
N-{4-merhoj^-7-[2-(6-merhyl-pyridm-3-yl)-t^
pyrrolidin- 1-yl-methyl-benzamide,
N-(4-methoxy-7-thiophen-2-yl-benzotlriazol-2-yI)^py^
N- [4-methoxy-7-(2~pyrio^-2-yI-thiazoI^yi)-beiizothia^ I -yi-
methyl-benzamide,
4-cUoro-N-(4-methoxy-7-morpholm-4-yl-ben201hiazol-2-yl)-3-pyrrohdm-l-yl-methyl-
benzamide,
N-(4-metho:^-7-morpholm-4-yl-benzothi^
N- (4-memoxy-7-morpholm^yl-beiizothiazol-2-yl)^(2-m
benzamide and
N-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-4- (4-methyI-piperazm- 1-yl-methyi)-
benzamide.
Especially preferred are compounds, wherein R4 is an optionally substituted five to seven membered aromatic or non aromatic heterocyde, which is for example morpholine or piperazine.
Preferred compounds of formula IA are those, wherein R1 is methoxy, X is oxygen andR2/R3 are hydrogen.
Exemplary preferred are compounds of formula IA, wherein R" is an unsubstituted or substituted five or six membered aromatic heterocyde, for example the following compounds: N-(4-me&oxy-7-morpholm^yl-berizotriiarol-2^

5~methyl-tHophene-2-carboxylic add (4-memoxy-7-phenyl-benzo1hiazol-2-yi)-arnide,
5-methyl~furan-2-carboxylic add f4-metho3cy-7-pb.en)^-benzothiazol~2-jd.)-amide>
N-(4-meliioxy"-7-phen^-benzo1iiiazol-2-yl)-isonicotinamide,
5-memyl-triiophene-2-carboxyiic add (4-memoxy-7-pyridm-4-yI-benzomiazol-2-yI)-
amide,
5-merayl-thiophene-2-carboxv]ic add (4-methoxy-7-pyridin-3-yi-benzothiazol-2-^)-
amide,
5~methyl~thiophene-2-carboxylic add [4-methoxy~7-(2-methyl-T^ridin-4-yl)-
benzothiazol-2-yl] -amide,
5-metbyl~thiopliene-2-carboxyiic add [7-(3-ammo-phenyl)-4-methoxy-benzothiazol-2-
yl] -amide,
N-(4-memoxy-7-tHophen-2-yl-benzothiazol-2-yl)-2-me^
N- [4r-methoxyr-7-(2-pyridm-2-yl-thiazoI-4-yl)-ben2otbiazol-2-yI] -2-methyl-
isonicotinamide,
N- [4-methoxy-7-(2-pyrrolidin- l-vl-tHazol-4-yi)-benzotaiazol-2-yl] -2-methyi-
isorucotinarnide,
N-{4-methoxy-7- [2-(4-methyl-piperazin-l -yl)-tniazoI-4-yl] -benzothiazol-2-yl}-2-methyl-isonicotinamide and
N- [4-metbox7-7-(5-metiiyl-"diiopheD-2-yl)-benzotbia2ol-2-yi] -2-mediyl-isonicotinamide.
Further preferred compounds of formula IA are compounds, wherein R is an unsubstituted or substituted five or six membered aon aromatic heterocyde, for example the following compounds:
morpholine-4-carboxylic add {4-methoxy-7-phenj4-benzothiazol-2-yl)-anude,
thiomorpholine-4-carboxyJic add (4-methoxy-7-pherryi-beiizotniazol-2-yl)-amide,
1-oxo-ll 4-thiomorphoune-4-carboxylic add (4-methoxy-7-phenyl-benzothiazol-2-yl)-
amide,
morphoBne-4-carboxylic add {4^mettoxy-7-[2-(6~memyl-pyridm-3-yl)-tbiazol-4-yl]-
benzothiazol-2-yl}-amide,
morpboline-4-carboxyUc add [4-me&oxy-7-(2-pyridm-2-yl-tinazol-4-yl)-berjzotbiazol-2-
yl]-amide,
morpholine-4-carboxyUc add {4-memoxy-7-[2-(4-methyl-prpera2m-l-yl)-thiazol-4-yi]-
benzomia2ol-2-yi}-amide1
morpholine-4-carboxyIic add [4^methoxy-7-(2-piperidm-l-yl-thiazol-4-yl)-benzotnia2ol-
2-yl]-amide,

morpholine-4-carboxylic acid [4-metboxy-7-(5-methyl-thiophen-2-yI)-ben20thiazol-2-
yl]-amide,
4-(4-memoxy-7-morpholm-4-yl-benzotm^2ol-2-yl-catbainoyl}-piperid^e-l-carboxyiic
acid tert-butyl ester,
l-acetyl-piperidine-4-carboxylic acid (4-memoxy-7-morpholin--4-yi-benzothiazoI-2-yl)-
amide,
4-oxo-piperidine-l-carboxylic acid (4-methoxy-7-morpholin-4-yl-beiizotbiazol-2-yl)-
amideand
l-oxo-lX4-tbJomorpholme-4-carboxylic acid (4-methoxy-7-prperidm-l-yI-ben2otbia2ol-
2-yl)-amide.
Preferred are further compounds, wherein R is methoxy, for example the following
compounds:
rac-[7-(2-bromo-l-hydroxy-emyl)-4-memoxy-benzotmazol-2-yl]-carbamic acid methyl
ester,
{4-methoxy-7-[2-(6-methyl-pyridm-3-yl)-tto
methyl ester,
[4-methoxy-7-(2-pyridm-2-yl-linazol-4-yl)-ber^ acid methyl ester,
[4-melho3cy-7-(2-piperidm-l-yl-miazol^yl)-benzothia2ol-2-yl]-carbamic acid methyl
ester and
{4-methoxy-7- [2- (4-methyi-piperarin- l-yl)-tniazol-4-yl] -benzothiazol-2-yl}-carbamic
acid methyl ester.
Preferred compounds of formula IA are those, wherein R1 is phenyl, optionally substituted by -CH2OH, -CH2NHCH2CH2OCH3, -CH2NHCH2CH2OH, -CH3NHCH2.-pyridinyl -CHsNH* -CH2NHCH2CH2SCH3, -CH2N(CH3)CH2CH2SCH3,-CH2N(CH3)CH2CH20CH3,
-CH2N(CH2 CH3)CH2CH2OCH3> -CH2NHCH3, -CHzSCHaCHzNfCHj)* -CHaOCHs, -CH2OCH2CH20CH3 or -CH2N(CH3)C(0)OCHj, for example the following compounds: 4-hydroxymethyl-N-(4-memoxy-7-phenyI-benzothiazoI-2-yI)-benzamide, 4- [ (2-methoxy-ethylamino)-methyl] -N-(4-methoxy-7-phenyI-ben2othiazol-2-yI)-benzamide,
4-[(2-hydrory-ethylamino)-memyl]-N-C4-methoxy-7-phenyl-benzothiazol-2-yl)^ benzamide,
N-(4-memoxy-7-phrayl-benzothiazol-2-yl)-4-{[(pyri benzamide,
N-(4-methoxy-7-phenyl-benzotmazol-2-yl)-4-{[(pyridm~3-ymiemyi)-ammo]-met^ benzamide,

4~aininometh^-N-(4-metiioxy"-7-phenyl-benzothiazol-2-ylJ-benzainKle, N-(4-methoxy-7-phenyl-benzothiazol-2-yi)-4- [(2~methylstilfenytediylamino)-methyl] -benzamide,
4-{[(2-methoxy-ethyl)-methyI-amino]-methyl}-N-(4-methoxy-7-morpholin-4-yi-benzothia2ol-2-yl)-benzamide,
N-[7-(2-ainino-thiazol^yl)^metiioxy-benzothiazol-2-yl]-4-fluoro-beiizainide, 4-fluoro-N-{4-methoxy-7- [2-(6-methyl-pyridin-3-yl)-thia2ol-4-yi] -benzotbjazol-2-yl}-benzamide,
4M[(2-methoxy-ethyi)-metiiyl-ainino]-meth^ yI)-thiazol-4-yl]-benzoliiiazol-2-yi}-benzamide,
4-{[(2-Methoxy-ethyl)-methyl-amino]-methyI}-N-(4-metimxy-7-diiopheD--2-yl-benzothiazol-2-yl)-benzamide,
4-{ [ (2-methoxy-ethyD-methyl-amino] -methyl}-N-[4-methoxy-7-(2-pyridiii-2-yl-thia2ol-4-yl)-benzotbia2ol-2-yI] -benzamide,
N-(4-methoxy-7-morpboUB-4-yl-berizoliia2oI-2-yI)^trifluorometbyl-ben2amide, N-(4-methoxy-7-morphoHn^yl-baizothia2ol-2-yi)-benzaniide,
4-cbloro-3-{[etiiyl-(2-meti.oxy-e&yI)-amino]-mediyI}-N-C4-metho^-7-moTpholiQ^yl-benzotiiiazol-2-yI)-beiizamide>
N-(4-metboxy,-7-morpholin-4-yl-ben2otbiazol-2-yi)-3-methylarninometbyl-benzam 4-cb]oro-N-(4-methc^-7-morpholk>4-yl-benzo^^ benzamide,
4-cUoro-3-{[(2-melitoxy-ethyl)-meiiyI-ainino]-meliiyi}-N-(4-metho^-7-taorpholin-4-yl-benzotbiazol-2-yl)-ben2amide>
4-cHoro-3-[(2-methoxy-ethykmino)-me1byI]-N-(4-methoxy-7-morphoIin-4-yl-benzothiazol-2-yI)-benzamide, 3-[(2-metboxy-etb.ylamino)-methyl]-N-(4-m yl)-benzamide,
3-{[(2-metboxy-ethyl}-methyl-amino]-methyl}-N-C4-medioxy-7-morpholiii-4-yi-benzothiazol-2-yi) -benzamide, 4-[(2-ethoxy-ethylainino)-methyl]-N-(4-me1hoxy^ benzamide,
N-(4-metbaxy-7-morpholin^)4-ben2odiiazoI-2-yl)-4-me&^ 4-(2-dimetbyIainino-e1bylsirifanyl^ 2-yl)-benzamide,
4-{[(2-ethoxy-etiiyl)-etbyl-amino]-metbyI}-N-(4-methoxy-7-morpho]iD^yi-benzothiazol-2-yl) -benzamide* 4-{[(2-elhoxy-ethyl)-methyl-ainino]-methyl}-N^^

benzothiazol-2-yl)-benzamide,
4-(2-methoxy-ethoxymethyl)-N-(4-^
benzamide,
4-memoxymethyl-N-(4-memoxy-7-mo:ipholm^yl-benz^
N-(4-methoxy-7-tbiomoipholin^-yl-benzotbia2ol-2-yl)-benzamideaiid
[4-(4-methoxy-7-morphoHn^yl-benzotiiiazol-2^
acid methyl ester.
Further preferred compounds of formula IA are those, wherein R" is phenyl, substituted by a optionally substituted -(CR^Vfive to seven membered aromatic or non aromatic heterocycle, for example the following compounds:
4-iimda2ol-l-yImemyl-N-(4-mefooxy-7-pta
4-(4-Hydro^-piperidm-l-yl-methyl)-N-(4-m
benzamide,
4-[l,4]diazepan-l-yl-memyl-N-(4rmethoxy-7-phenyl-benzotbiazol-2-yl)-ben2am^
4-( 3 (S)-dimethylammo-pyiToHdm-l-yl-memy
yl)-benzamide,
N-{4-metboxy-7- [2-( 6^memyl-pyridin-3-yi)-tbiazol-4-vl] -benzothiazol-2-yl} -4-
pyrrolidin-1-yl-methyl-benzamide,
N-(4-methoxy-7-thiophen-2-yl-benzothiazol-2-yl) -4-pyrrolidin- l-yl-methyl-benzamide,
N-[4-memoxy-7-(2-pyridm-2-yI-tbiazoI^yI)-beiizothia^
methyl-benzamide,
4-chloro-N-(4-metiioxy-7-morpholm^yl-benzotbia2ol-2-yI)-3-pyrroKam
benzamide,
N- (4-memoxy-7-morpholm^yl-benzo1hia2ol-2-yl)-3-pyrrolidin-l -yl-medrjd-benzaniide,
N- (4-memoxy-7-morpholm^yl-benzothiazol-2-yl)-4-(2-methyl-imidazol-1 -yl-methyl)-
benzamide and
N- (4~memoxy-7-morpholm^yl-benzothiazol-2-yl)-4-(4-methyl-piperazin- l-yl-methyl)-
benzamide.
Especially preferred are compounds of formula IA, wherein R4 is an optionally substituted five to seven membered aromatic or non aromatic heterocycle, which is for example morpholine or piperazine.
The present compounds of formulas I and I-A and their pharmaceuticafly acceptable salts can be prepared by methods known in the art, for example, by processes described below,

if desired, converting the compounds obtained into pharmaceuticaUy acceptable acid addition salts.
All reaction steps described above are carried out in conventional manner and are described in more detail in the working examples.
In accordance with process variant a) a compound of formula II, for example 2-amino-7-phenyl-4-niethoxy-ben20tbiazol in pyridine is dissolved in tetrahydrofuran and is then treated with phosgene in toluene. The reaction mixture is concentrated to half the volume under reduced pressure and the appropiate amine, for example an amine of formula R5R6NH or a cyclic amine, such as morpholine or thiomorpholine, are added. The obtained product is isolated by flash chromatography.
Reaction variant b) describes the process for preparation of a compound of formula I, wherein a compound of formula II is reacting with a compound of formula IV. The reaction is carried out for about 10 minutes in conventional manner. The obtained compound is then isolated by flash chromatography.
The salt formation is effected at room temperatures in accordance with methods which are known per se and which are familiar to any person skilled in the art. Not only salts with inorganic acids, but also salts with organic acids came into consideration. Hydrochlorides, hydrobromides, sulphates, nitrates, citrate, acetates, maleates, succinates, methan-sulphonates, p-toluenesulphonates and the like are examples of such salts.
In Examples 1 —187 and in the following schemes 1 and 2 the preparation of compounds of formula I is described in more detail.
The starting materials are known compounds or may be prepared according to methods known in the art.

compounds of the present invention may be useful as sedatives, muscle relaxants, antipsychotics, antiepileptics, anticonvulsants and cardiaprotecuve agents and for the production of corresponding medicaments.
The most preferred indications in accordance with the present invention are those, r which include disorders of the central nervous system, for example the treatment or prevention of certain depressive disorders, neuroprotection and Parkinson"s disease.
The dosage can vary within wide limits and will, of course, have to be adjusted to the individual requirements in each particular case. In the case of oral administration the dosage for adults can vary from about 0.01 mg to about 1000 mg per day of a compound of general formula I or of the corresponding amount of a pharmaceutically acceptable salt thereof. The daily dosage may be administered as single dose or in divided doses and, in addition, the upper limit can also be exceeded when this is found to be indicated.
Example 1
N- (4-Memoxv-7-phenyl-benzothiazol~2--vl) -benzamide
To a solution of 2-animo^methoxy-7-phenyl-benzothiazole (100 mg, 0.4 mmol) in pyridine (2 ml) was added benzoyl chloride (55 mg, 0.4 mmol) and the mixture stirred overnight at 20 °C. To this mixture 2N HC1 to pH 1 (20 ml) was added then the mixture was extracted twice with EtOAc (20 ml), washed with saturated NaHCC>3 solution, dried with NajS04 and the solvent evaporated. The crude product was then chromatographed over Si02 (Merck 230-400 mesh) eluting with Ct^CVMeOH (98:2), the product fractions were pooled and the solvent evaporated, to afford the title compound as a white solid (97 mg, 69 % yield), MS: m/e=360 (M*).
Following the general method of example 1 the compounds of examples 2 to 49 were prepared
Example 2
FuTan-2-carboxvuc acid (4-methoxv-7-phenyl-benzothia2ol-2-ylVamidfc
Using furan-2-carboxylic acid chloride the title compound was prepared as a beige solid (41 % yield), MS: m/e= 251.3 (M+lT).
Example 3
5-Methvl-|^|nphene-g-carbo3cy]jc acid f4-methoxy-7-phenvl-b^79*bia;zoI-2-yD-aTTiide

Using 5-methyi-diiophene-carbozylic acid chloride the title compound was prepared as a beige solid (36 % yield), MS: m/e= 381.3 (M+H+).
Example 4
Furan-2-carboxviic acid (4,6-difluoro-berizothiazol-2-yl)-arnide
Using 2-amino-4,6-difluoro-benzothiazole and fUran-2-carboxyiicacid chloride the title compound was prepared as a grey solid (81 % yield), MS: m/e= 280 (M1").
Example 5 5-Methyi-thiophene-2"Carbox>dic acid (4,6rdifluoro-benzothifl7-n)-^-yT)-amiHg
Using 2-ammo^,6-^lifluoro-benzothiazoIe and 5-methyl-thiophene-carboxylicacid chloride the title compound was prepared as a yellow solid (74 % yield), MS: m/e= 310
Example 6
N- (4,6-Difluoro-benzothiazol-2-yl)-benzamide
Using 2-arnino-4,6-difluoro-benzothiazole and benzoyl chloride the title compound was prepared as a beige solid (82 % yield), MS: m/e= 290 (M*).
Example 7
N-(4-Methoxv-7-phenvl-beiizothiazol-2-yl)-acetamide
Using acetyl chloride the title compound was prepared as a light brown solid (69 % yield), MS: m/e= 299.2 (M+JT).
Example 8 4-Cyano-N-f4-methoxv-7-pheayl-benzothiazol-2-yl)-benMrnidft
Using 4-cyaho-benzoyl chloride the title compound was prepared as yellow solid (84 % yield), MS: m/e= 385.1 (M*).
Example 9
5-Methyl-thiophene-2-carboxvlic acid f4-methoxy-h"i7^hiq2ol-2-yl)-amide

Using 2-ainino-4-methoxy-benzothiazole and 5-methyi-thiophene-2-carboxylic acid chloride in pyridine the title compound was obtained as a beige solid (95 % yield), MS: m/e=304.1 (M*).
Example 10
5-Methvl-furan-2-carboxviic acid (4-methoxy-7-phenyl-benzothia2ol-2-vlVamide
Using 2-amino-4-methoxy-7-phenyl-benzothiazole and freshly prepared 5-methyl-fhran-2-carboxylic acid chloride the title compound was obtained crude, which was chromatographed over S1O2 (Merck 230-400 mesh) during with nHexane/EtOAc (4:1), to afford the pure title compound as a pale yellow solid (67 % yield), MS: m/e=364.0 (M*).
Example 11
Furan-2-carboxylic acid f 4-memoxv-berizo1niazoI-2-yO-amide
Using 2-amino-4-methoxy-benzothiazole and furan-2-carboxylic acid chloride in pyridine the title compound was obtained as a tan solid (100 % yield), MS: m/e=274.1 (M*).
Example 12 N-(4-Methoxy-benro1hiazol-2-ylVben2ainide
Using 2-amino-4-methoxy-benzotbiazole and benzoyl chloride in pyridine the tide compound was obtained as a white solid (72 % yield), MS: m/e=284.1 (M*).
Example 13
Benzo[b]thiophene-2-carboxvh^acidben7nthia7nV2-ylamide
Using 2-amino-benzothiazole and benzo[b]thiophene-2-carboxyhc acid chloride in pyridine the title compound was obtained as a light yellow solid (86 % yield), MS: m/e=311.1 (M+fT).
Example 14
3-Methyl-lbiophene-2-carbpxylic arid henvrithiavcA-J.-ylamicip.
Using 2-amino-benzothiazole and 3-methyl-thiophene-2-carboxylic acid chloride in pyridine the title compound was obtained as a yellow solid (69 % yield), MS: m/e=275.1 (M+H*).

Example 15 5-Methyl-thiophene--2-caiboxvIic acid benzothiazoI-2-yIamidfi
Using 2-amino-benzothiazoIe and 5-mimyl-thiophene-2-carboxyhc acid chloride in pyridine the tide compound was obtained as a yellow solid (87 % yield), MS: m/e=275.1
(M+H*).
Example 16 N-Benzothiazol-2-^-6-chloro-nicntinamide
Using 2-araino-benzomiazole and 2-chloropyridine-5-carboxylic acid chloride in pyridine die title compound was obtained as a white solid (97 % yield), MS: m/e=290,l (M+H*).
Example 17
4-Hvdroxymethyl-N- (4-memoxv-7-phenvi-benzolhiazol-2-vl"}-benzamide
To a solution of 4-fbrmyl-N-(4-methoxy-7-phenyl-ben2othiazol-2-yl)-benzamide (194 mg, 0.5 mmol), in THF (40 ml) was added sodium borohydride (19 mg, 0.5 mmol) and the mixture stirred for 2 h at r.t. Water was added (30 ml) followed by IN HC1 (4 ml) and the mixture agitated. The aqueous phase was then extracted twice with EtOAc (30 ml), the combined organic phases were then washed with saturated NaCl solution, dried with NasS04 filtered and evaporated. The crude residue was suspended in ether and ultrasonnicated for 10 min-, the solid precipitate was filterted off, washed with ether then dried under vacuum (0.05 mmHg, 50 °C) to afford the title compound as a light yellow solid (150 mg, 77 % yield), MS: m/e= 390.0 (M*).
Example 18
4-Formyl-N-(4-me&oxv-7-phenyl-beigotbia2ol-2-v^""-t\ Using 4-formyl benzoic add the title compound was obtained as a light yellow solid (73 % yield), MS: m/e=388.1 (M+H*).
Example 19 2-Memoyy-N-(4-methoxy-7-phenvl-ben20thiazol-2--vlVbf!n7arni^f-
To a solution of 2-amino-4-methoxy-7-phenyl-benzothiazole (200 mg, 0.67 mmol) in THF (10 m) was added DMAP (10 mg, 0.08 mmol), triethylamme (163 pi, 1.17 mmol) and 2-m**boxybeim37lchkmdetl36MKlmiTw>i)mT

reflux for 2 h, after cooling, it was partitioned between 1:1 AcOEt/THF (70 ml) and 5% NaHC03 solution( 40 ml). The organic phase was washed with saturated NaCl solution (50 ml), dried with Na2S04, filtered and the solvent removed under reduced presure. The residue was suspended in ether (10 ml), filtered, washed with ether then dried under vacuum (0.05 mmHg, 60 °C), to afford the title compound was a white solid (260 mg, 85 % yield), MS: m/e= 390.0 (M*).
Example 20
N-f4-Meriiogy-7-phenvl-beiizothiazoI-2-vl)-2-metliyl--benzarnide
Using 2-methyl-benzoyI chloride the title compound was obtained crude, which was chromatographed over Si03 (Merck 230-400 mesh) eluting with O^CVEtOAc (1:1), to afford the pure title compound as a white solid, (88 % yield), MS: m/e=374.3 (ht).
Example 21
N-f4-Metlioxy-7-phenyl-benzothiazol-2-ylV3-meth.Yl-benzamide
Using 3-methyl-ben2oyl chloride the title compound was obtained crude, which was chromatographed over Si02 (Merck 230-400 mesh) eluting with Cf^CVEtOAc (1:1), to afford the pure title compound as a light yellow solid, (80 % yield), MS: m/e=374.0 (M1").
Example 22 N-(4~Metlioxv-7-pheny]-hffn7omiazol-2-yl^-4-meth.yl-bgn7aTTiiHf;
Using 4-methyi-benzoyl chloride the title compound was obtained crude, which was chromatographed over Si02 (Merck 230-400 mesh) eluting with CH2Cl2/EtOAc (1:1), to afford the pure title compound as a white solid, (79 % yield), MS: m/e=374.1 (M*).
Example 23
4-Huoro-N-f4-memoxv-7-pheriyI-benzotriiazol-2-yl)-ben2arnide
Using 4-fluoro-benzoyl chloride the title compound was obtained crude, which was chromatographed over SiC^ (Merck 230-400 mesh) eluting with CHzCb/EtQAc (1:1), to afford die pure title compound as a white solid (68 % yield), MS: m/e=378.0 (M*).
Example 24 3-Memoxv-N-("4-methoxy-7-phenyl-^*"7-"t^ia7ol-2-yl)-hen»aTniHf"

Using 3-methoxy-benzoyl chloride the title compound was obtained crude, which was chromatographed over Si02 (Merck 230-400 mesh) eluting with CH2Cl2/EtOAc (1:1), to afford the pure title compound as a light yellow foam (75 % yield), MS: m/$=390.0 (M*).
Example 25
4-Methoyy-N-(4-memoxy"7-phenyl-benzotJiia2ol-7-y1)-hnMTTiiHi»
Using 4-methoxy-benzoyl chloride the title compound was obtained crude, which was chromatographed over Si02 (Merck 230-400 mesh) eluting with CH2Cl2/EtOAc (1:1), to afford the pure title compound as a white foam (79 % yield), MS: m/e=390.i (M*).
Example 26
N-(4-Methoxy-7-phenyl-benzothiazol-2-vl)-2-phenyl-acetamide
Using phenylacetyl-chloride chloride the tide compound was obtained crude, which was chromatographed over Si02 (Merck 230-400 mesh) eluting with CH2Cl2/EtOAc (1:1), to afford the pure tide compound as a white solid (29 % yield), MS: m/e=374.1 (M*).
Example 27
3-Methvl-thiophene-2-carboxyiic acid (4-metboxy-7-phenyl-benzothiazoi-7.-yT)-aTniHf»
Using 3-in^yJ-tbj0ribrae-2-carbaxylicarid chloride tie title compound w&s obtained crude, which was chromatographed over Si02 (Merck 230-400 mesh) eluting with CEbCh/EtOAc (1:1), to afford the pure title compound as a white solid (64 % yield), MS: m/e=380.0 (M+).
Example 28
2,5-Dimethyi-fttran-3-carboxjdic acid (4-memoxy-7-phenyl-benzothia2oI-a-Yl)-amirie
Using 2,5-dimemyl-furan-3-carboxylicaad chloride the tide compound was obtained crude, which was chromatographed over Si02 (Merck 230-400 mesh) elutiiig with CH2Cl2/EtOAc (1:1), to afford the pure tide compound as a white solid (73 % yield), MS: m/e=378.1 (M+).
Example 29 3-Cyano-N-f4-methoxy-7-phenyl-benzothiazol-2-yl^-bCTi7aiTiiflp

using ^-cyano-benzoyl cnlonde toe title compound was obtained crude, which was chromatographed over Si02 (Merck 230-400 mesh) eluting with CH2Cl2/EtOAc (1:1), to afford the pure title compound as a white solid (80 % yield), MS: m/e=385.0 (M+).
Example 30
" N-f4-Methoxy-7-phenoyy-benzomiazol-2-1id)-benzamide
Using 4-Memoxy-7-phenoxy-beiizothiazol-2-ylamine and benzoyl chloride the title compound was obtained crude, which was chromatographed over Si2 (Merck 230-400 mesh) eluting with CrkCU/EtOAc (1:1), to afford the pure title compound as a white solid (72 % yield), MS: m/e=376.1 (M*)-
Example 31
4-Dimemykmmo-N-(4-methor^-7-pheDvI-ben2adiiazol-2-vl)-benzarnide
Using 4-dimethylamino-benzovl chloride in pyridine the title compound was obtained crude, which was chromatographed over Si02 (Merck 230-400 mesh) eluting with CH2CV(2N NH3inMeOH) (19:1), to afford the pure title compound as a beige solid (70 % yield), MS: m/e=403.0 (M*").
Example 32
4-Huoro-N-(4-methoxy-7-phenyl-bpTi?r>t^iqzol-2-ylVN-metfav^-Vipn7-flTrii^e
Using (4-nimethoxy-7-phenyl-benzo11uazol-2-yl)-methyl-amine and 4-fluoro-benzoyl chloride in pyridine the title compound was obtained crude, which was chromatographed over Si02 (Merck 230-400 mesh) eluting with CH2Cl2/EtOAc (1:1), to afford the pure title compound as a beige solid (88 % yield), MS: m/e=393.2 (M+H*).
Example 33
2-(4-HuorcHbeng^aTninn^-4-memoxv-benzolfaiazole-7-carboxyhc acid methyl ester
Using 2-ammo-4-medioxy-benzothiazole-7-carboxyhc acid methyl ester and 4-fluoro-benzoyl chloride the title compound was obtained as a white solid (91 % yield), MS: m/e=361.1 (M+H+).
Example 34 N-f7-teit-Bu1vl-4-memoxy-beriZ01hiazol-2-vl)-4-fluoro-benzarnide

I "
Using 7-tert-butyl-4-memoxy-benzothiazol-2-ylarnine and 4-fluoro-benzoyl chloride die tide compound was obtained as a white solid (75 % yield), MS: m/e=258.1 (M+H*).
Example 35
N-f7-Acel7^airiiTio-4-mel3ioxv-benzotmazol-2-yl)^"fluoro-benzamide
Using 7-acetylammo-4-memoxy-benzothiazoI-2-ylamrne and 4-fluoro-benzoyl chloride the title compound was obtained as a tan solid (25 % yield), MS: m/e=359.1 (M+H*).
Example 36 N- (4-Methoxy-7-phenyl-beHzothiazol-2-yt1-isonir-ntinamiH e
Using pyridine-4-carboxyiic acid chloride hydrochloride salt in pyridine the tide compound was obtained crude. After cooling a solid precipitated from the reaction mixture which was further triturated with ether (10 ml) then collected on a glass sinter and further washed with ether (10 ml). The filter cake was then washed sequentially with 10% Na2C03 (20 ml), water (20 ml) followed by ether (20 ml) and the resulting product dried under vacuum (0.05 inmHg, 60 °C) to afford the pure title compound as a yellow solid (188 mg, 67 % yield), MS: m/e=361.0 (M+).
Example 37 4-Fluoro-N- (4-metfaoxy-7-phenoxy-beri7.othia7.nl -2-yl)-benzamide
Using 4-metiioxy-7-phenoxy-benzothiazol-2-ylamine and 4-fluoro-benzoyl chloride the title compound was obtained crude, which was chromatographed over SiC>2 (Merck 230-400 mesh) eluting with CH^Cb/EtOAc (1:1), to afford the pure title compound as a white solid (75 % yield), MS: m/e=394.1 (M+).
Example 38
5-Methyl-thiophene-2-carboxyIic acid (4-methoxv,-7-phenoxv-benzotbia7.ol-2-vIVamide
Using 4-metJioxy-7-phenoxy-benzothiazol-2-viarnine and 5-methyl-thiophene-2-carboxyhc acid chloride the title compound was obtained crude, which was chromatographed over Si02 (Merck 230-400 mesh) eluting with CHjCb/EtOAc (1:1), to afford the pure title compound as a pale yellow solid (76 % yield), MS: m/e=396.0 (M*").
Example 39
4-Huoro-N-(4-methoxv-7-morpholm-4-ylmefryl-ben?^^

Using 4-meth.oxy-7-morpholin-4-ylmethyI-ben20t}iiazol-2-yiamiiw and 4-fluoro-benzoyi chloride in pyridine the title compound was obtained as a yellow solid (44 % yield), MS: m/e=402.4 (M+H*).
Example 40
5-Metbyl-tbjophene-2-carboxvlic add (4-methoxv-7-morphn1in-4-vlinethvi-benzothiazol-2-yl)-amide
Using 4-methoxy-7-morphoiin-4^ylmethyl-beDaotMazoI-2-ylanune and 5-methyi-tbiophene-2-carboxyUc add chloride in pyridine the title compound was obtained as a yellow solid (53 % yield), MS: m/e=404.4 (M+H1").
Example 41
4-Huoro-N-[4-memoxv-7-flH-telTa2ol-5-yl)-benzo1luazol-2-yl1-benzamide
Using 4-methoxy-7-( lH-tetrazol-5-yl)-beiizotniazol-2-ylamine and 4-fluoro-benzoyl chloride in pyridine the title compound was obtained as a tan solid (70 % yield), MS: m/e=371.2 (M+H*).
Example 42
N-BenzotHa"ml-3-vl-benzamide
Using 2-amino-benzothiazole and benzoyl chloride in pyridine the title compound was obtained as a white solid (87 % yield), MS: m/e=255.1 (M+H*).
Example 43
Furan-2-carboxyiic add benzothiazol-2-ylamide
Using 2-amiho-benzothiazole and furan-2-caiboxylic add chloride in pyridine the title compound was obtained as a white solid (83 % yield), MS: m/e=244 (M*).
Example 44
2-CMoro-N-(4-meth^-2-benzotfaiazoIyi)-nicotinamide
Using 4-memyl-benzothia2ol-2-ylamine and 2-chloronicotinic add chloride the title compound was obtained as a yellow solid (50% yield), MS: m/e= 304 (M+H1-).

Jsxampie4D
2"chloro-N-f4-memoxy-2-beiizothia2oM-nicotinamide
Using 4-memoxy-benzothiazol-2-yiamine and 2-chloronicotinic acid chloride the title compound was obtained as a off-white solid (50% yield). MS: m/e= 320 (M+H1-).
Example 46
3-f4-Memoxv-bem^tbiazol-2-ylcarbarooyl)-acrylicacid ethyl ester
Using 4-metiioxy-ben2otmazol-2-ylamine and 3-chlorocarbonvl-acryiic acid methyl ester the title compound was obtained as a off-white solid (50% yield). MS: m/e= 307 (M*).
Example 47
N-(4-Methoxy-7-phenyl-beny.othiazol-2-yl)-nyalaTnir acid ethyl ester
The tide compound is described in the following patent literature and was prepared according to the procedure described therin. N-(Benzothiazol-2-yl)oxamic add derivatives. W. Winter, M. Thiel, A. Roesch and O. H. Wflnelms, German Patent, DE 2656468,1978. Up, 138-J42°C,MS: m/e=357 (M+H*).
Example 48
4-nimfthylaTYimo-N-(4-methoxy-7-phenyI-benzothiazoI-2-yl)-bertzarmde
Using pyridine-2-carboxyUc acid, chloride hydrochloride salt in pyridine the title compound was obtained crude. This compound was purified further with preparative reversed phase HPLC using a Nucleosil N-proteced column (20 mmx50 mm) and eluting with a gradient of MeCN/ water (0.1 % TFA), The product fractions were pooled, evaporated and the residue partitioned between EtOAc (30 ml) and 10 % Na2C03 (30 ml) and the aqueous phase extrteacted once with EtOAc (30 ml) The combind organic phases were then washed with satuarated NaC3,.dried, fitered and evaporated to afford the pure title compound as a beige solid (110 mg, 39 % yield), MS: m/e=361.1 (M1").
Example 49
4-Fluoro-N-( 7-hydroxymetiiYl-4-methoxv-benothiazol-2-yl )V>pn7amide
To a solution of 2-(4-fluoro-beri2oylammo)^methoxy-beiizotniazole-7-carboxyiic acid methyl ester (1.1 g, 3.05 mmol) in THF (250 ml) uner argon at 5 «C was added a solution of !NIiAlr^mTrg(2mr,2mTM*)oTcr5-inm.,t^

then over 1 h allowed to warm to 20 °C. A further 3.5 ml of IN LiAIIVTHF was then added dropwise and the mixture stirred a further 2h at 20 °C. A solution of 5 ml THF/Water (4:1) was then added cautiosly followed by 4N NaOH (2 ml), then water (2 ml) and the mixture stirred vigorously for 15 min. Excess Na2S04 (50 g) was then added with vigorous stirring, then the solution was filtered and the solvent evaporated to afford fher title compound as a white solid (0.9 g, 89 % yield), MS: m/e=333.2 (M+H*).
Example 50
4-Dipropylsn1fiiTTioyl-N-f4-methoxy-7-phenvl-benzo1hia2ol-2-yl)-H*^yaTnide
To a suspension of 4-dipropyisulramoyi-benzoic acid (185 mg, 0.65 mmol) in toluene (10 ml) was added thionylchloride (600 mg, 5 mmol) and the mixture heated to 80 °C for 17 h. After cooling the solvent was evaporated and the resudue was taken up in THF (20 ml), 2-arrn^c^-memoxy-7-phenyl-ben2othiazole (128 mg, 0.5 mmol), triethyiarnme (105 ul, 0.75 mmol), and DMAP (6 mg, 0.05 mmol) were then added and the mixture was stirred for 1 hour at r.L followed by 1 hour at 60 °C. After cooling to r.t the reaction raixture was quenched by addition of 10 % aq. Na2C03 solution (30 ml) and EtOAc (30 ml) and vigorous stirring. After separation of the phases the aqueous phase was extracted with EtOAc (30 ml) and the combined orgainc phases were washed with 10 % aq. Na2C03, dried with NaaSCU, filtered and evaporated. The residue was then chromatographed over Si02 (Merck 230-400 mesh) eluting with a gradient of cydohexane/EtOAc from (1:4) to 100 % EtOAc. After pooling and evaporation of the product fractions the title compound was obtained as a white solid (240 mg, 92 % yield), MS: m/e=524^ (M+rT).
Following the general method of example 50 the compounds of examples 51 to 53 were prepared
Example 51
4-Diemylsuifamovl-N-f4-memoxv-7-phenYl-bertzotm^ol-2-yJ)-bfm7amiHe
Using 4-diethylsulfamoyl-ben2oic acid the title compound was obtained as a light yellow solid (81 % yield), MS: m/e=496.2 (M+rT).
Example 52
N-(4-Memoxv-7-phenvl-benzothiazol-2-yl)^(morphn1me^sulfonvlVbenzamide
Using 4-(morpriomie^sulfonyl)-benzoic add the title compound was obtained as white amorphous solid (32 % yield), MS: m/e=510.3 (M+rT).

Example 53
4-£th^dsuIfamovI-N-f4-methoxy-7-phenyi-benzothiazoI-2-yI)-benzamide
Using 4-ethylsulfamoyl-benzoic add the title compound was obtained as pale yellow amorphous solid (20 % yield), MS: m/e=4662 (M-H)".
Example 54 5-Methyl-fliiophene-2-carboxYUc add f 7-iodo-4-memoxy-benzothiazol-?.-v1)-amid*"
lodination of 5-methyl-thiopliene-2-carboxyiic add (4-methoxy-benzothia2ol-2-yl)-amide (5.17 g, 17 mmol) with iodine monodiloride (2.26 ml, 44 mmol), sodium acetate (3.63 g, 44 mmol) and acetic add (200 ml) in the same manner as described for (4-methoxy-benzothiazol-2-yl)-carbamic add methyl ester affords the product as off-white solid in 93% yield. MS: m/e= 430 (M*).
(7-Aryl-4-methoxy-ben2othia2ol-2-yI)-carbamic add ester, aryl-carboxylic add (7-aryl-4-methoxy-benzothiazol-2-yl)-amides and substituted (4-memoxy-7-aryl-benzQthiazol-2-
yl)-ureas:
General procedure A: (7-Iodc«4-methoxy-benzothiazol-2-yl)-carbamic add ester or the respective aryl-carboxylic add (7-iodo-4-memoxy-benzothiazol-2-yI)-amide or the respective (4-methoxy-7-aryl-benzothiazol-2-yI)-urea (1 part), the appropriate boronic add (or its ester) (1.5 equivalents), palladium(II) acetate (0.05 equivalents), potassium phosphate (2.5 equivalents) and 2-biphenyl-dicydohexyl phospbine (0.1 equivalents) are combined in toluene (20 parts) and heated in an atmosphere of argon to 65 °C for 12 hours. The reaction mixture is evaporated to dryness and the product isolated by flash chromatography (silica, eluent ethyl acetate/cydohexane 2:1).
General procedure B: (7-Iodo-4-memoxy-beri2othiazol-2-yl)-carbamic add ester or the respective aryl-carboxylic add (7-iodo-4-methoxy-benzorhiazoI-2-yl)-amide amide or the respective (4-memoxy-7-aryI-berizothiazol-2-yl)-urea (1 part), the appropriate aryltrimethylstannane (1.5 equivalents), triphenylarsine (0.5 equivalents), tris-(dibenzylideneacetone)-dipalladium(O) (0.8 equivalents) and copper(I)iodide (0.8 equivalents) are combined in dirnethylformamide (25 parts) and heated to 80 °C for 12 hours. The reaction mixture is evaporated to dryness and the product isolated by flash chromatography (silica, eluent ethyi acetate).

Following the general method the compounds of examples 55 to 62 were prepared
Example 55
5-Methvl-thiophene-2-carboxylic add r7-f2-diloro-phenvD-4-methox7-benzothiazol--2-vl] -amide
5-MethyI-thiopbene-2-carboxyUc add [7-(2-chloro-phenyl)-4-methoxy-benzothiazol-2-yi]-amide is synthesized from 5-methyi-thiophene-2-carboxyiic add (7-iodo-4-methoxy-benzothazol-2-yl)-amidie (100 mg, 0.23 mmol) and 2-chlorophenylboronic add (54 mg> 0.35 mmol) using the general procedure A as a light yellow solid in 80% yield. MS: m/e=
415 (M+H+).
Example 56
5-Methyl-thiophene-2-carbo3ndic add [4-methoxy-7-(3-nitro-phenyi)-bengftfbifl7.Al-?-yt"j -amide
5-Methyl-thiophene-2-carboxyiic add [7-(3-nitro-phenyl)-4-methoxy-benzotbia2ol-2-yl]-amide is synthesized from 5-memyl-thiophene-2-carboxyiic add (7-iodo-4-methoxy-benzothiazol-2-yl)-amide (155 mg, 0.36 mmol) and 3-nitrophenyIboronic add (135 mg, 0.81 mmol) using the general procedure A as alight yellow crystalls in 42% yield. MS: m/e= 425 (M4").
Example 57
5-Methyi-tfaiophene-2-carboxvuc add f743-dimettvyfoTTiiffo-phenvD-4-methoxy-benzo-thiazol-2-Yl] -amide
5-Methyl-tbiophene-2-carboxyUc add [7- (3-dimethylarnino-phenyl)-4-methoxy-benzothiazol-2-yl] -amide is synthesized from 5-methyl-thiophene-2-carboxyiic add (7-iodo-4-metiioxy-berizotbiazol-2-yl)-amide (100 mg, 0.23 mmol) and 3-dimediylaminophenylboronic add (58 mg, 0.35 mmol) using the general procedure A as a light yellow solid in 71% yield. MS: m/e= 424 (M+rT).
Example 58
5-Methyl-i"biopbene-2-carboxylic add (4-methoxy-7-pvri6m.-4-yl-ben7x)thiazol-2-vl)--amide
5-Methyl-thiophene-2-carboxylic add (4-methoxy-7-pyridin-4-yi-benzothiazol-2-yl)-amide is synthesized from 5-methyl-tibiophene-2-carboxyHc add (7-bromo-4-methoxy-

benzomiazol-2-yl)-amide (192 mg, 0.50 mmol) and 4-pyridyIboronic acid (92 mg, 0.75 mmol) using the general procedure A as a white solid in 6% yield. MS: m/e^ 381 (M*).
Example 59
5-Memyl-thiophene-2-carboxyUc acid f4-memoxv-7-pvridin-3-yl-benzoniiazol-2-Yl"l-amide
5-Methyl-thiophene-2-carboxylic acid (4-memoxy-7-pyridin-3-yi-berizothiazol-2-yl)-amide is synthesized from 5-methyi-tbiophene-2-carboxyiic add (7-bromo-4-methoxy-benzothiazol-2-yl)-amide (192 mg, 0.50 mmol) and 4-pyridyiboronic acid (123 mg, 1.0 mmol) using the general procedure A as a white solid in 8% yield. MS: m/e= 381 (M*).
Example 60
5-Methyi-thiophene-2-carboxylic acid f4-metfaoyv-7-pyridin-2--yl-ben7ntHia7.nl-2-yl"l-amide
5-Methyl-thiophene-2-carboxylic acid (4-methoxy-7-pyridm-2-yl-benzothiazol-2-yl)-amide is synthesized from 5-methyl-thiophene-2-carboxylic acid (7-iodo-4-methoxy-benzotiuazol-2-yl)-ainide (100 mg, 0.23 mmol) and 2-tri-n-butylstannane (130 mg, 035 mmol) using the general procedure B as a white solid in 23 % yield. MS: m/e= 382 (M+H*).
Example 61
5-Methyl-thiophene-2-carboxybc acid [4-methoxy-7-f2-methyl-pyriflin-4-v^V hpn?nthia7.o1 -2-y!] -amide
5-Methyl-thiophene-2-carboxyUc acid [4-methoxy-7-(2-methyl-pyridin-4-yI)-benzothiazol-2-yl]-amide is synthesized from 5-memyl-thiophene-2-carboxyuc acid (4-meuioxy-7-iodo-benzothiazol-2-yl)-amide (260 mg, 0.60 mmol) and 2-methyl-4-trimethylstannanyl-pyridine (384 mg, 0.90 mmol) using the general procedure B as a light yellow solid in 50% yield. MS: m/e= 396 (M+H*).
Example 62
5-Memyl-thmphene-2-carboxvlic acid [7-f3-amino-phenvl)-4-metho]ry-ben?.r>thTazol-2-yil-amide
5-Methyl-thiophene-2-carboxyiic acid [7-(3-ammo-phenyl)-4-memQry-benzothiazol-2-yl]-amide is synthesized from 5-methyl-thiophene-2-carboxylic add (4-methoxy-7-iodo-

benzotbiazol-2-yl)-ainide (300 mg, 0.70 mmol) and 3-trimethylstannanyl-phen,jdamine (291 mg, 1.14 mmol) using the general procedure B as a light brown solid in 56% yield.
MS: m/e= 396 (M+it).
Example 63 5-Methvi-thiophene-2-carboxyhc add f4-hvdroxy-7-phenvi-benzothia7-nl-?.-y1)-anniHp
A solution of 5-methyl-thiophene-2-carboxylic add (4-methoxy-7-phenyl-benzodiiazol-2-yi)-amide (630 mg, 1.7 mmol) is slowly trated with boron tribromide (16 ml, 1.0 M in dicbloromethane) at 0 °C. The reaction is slowly wanned to ambient temperature and stirred for further 72 h. The mixture is diluted with ethyl acetate and extracted twice with water and once with brine. After drying over sodium sulfate, the solvent is removed in vacuo. Hash chromatography (silica, eluent ethyl acetate/hexane 1:1) and final recrystallization from tetrahydroforane/hexarie yields 118 mg (19 %) of the product as white solid. MS: m/e= 367 (M+H*).
Example 64
4-l4-Methoxy-2-ff5-memyl-truophene-2-carbonvl)-ammo|-benzomiazoI-7-yll-pipf»r37ine-l-carbQxylic add benzyl ester
The title compound was synthesized starting from N-benzyloxycarbonylpiperazine and 4-bromo-2-mtroanisole as described for 5-methyl-thiophene-2-carboxylic add (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide and obtained as a white solid in 12 % overall yield, MS: m/e= 523 (M+H*).
Example 655-Methvi-thiophene-2-carboxvlic add f7-f3-dimemviamino-pyrrolidiTi-1-yi^-4-metho3cy-benzothiazol-2-yl1 -amide
The title compound is synthesized starting from 3-(dimetn)iamino)pyrrolidine and 4-bromo-2-nitroanisole as described for 5-methyl-thiophene-2-carboxylic add (4-methoxy-7-moipholm-4-yl-b«nzothiazol-2-yl)-amide and was obtained as yellow solid in 10% overall yield, MS: m/e= 417 (M+H*).
Example 66
5-Methvl-tbiophene-2-carboxyhc add f5-memoxv-7-Dhenvi-benzothia2ol~2-vl)-arnide
2-Amino-5-methoxy-7-phenyIben20thiazol (45 mg, 0.18 mmol) is dissolved in dichloromethane (2 ml) and subsequently treated with triethylamine (0.073 ml, 0.53 mmol) and 5-methyl-thiophene-2-carbonyl chloride (56 mg, 0.35 mmol). After 6 fa,

further 0.073 ml, 0.53 mmol) and 5-methyi-thiophene-2-carbonyl chloride (56 mg, 035 mmol) are added and the mixture is stirred for additional 18 h at ambient After addition of 0.1M aqueous sodium hydroxide, the mixture is stirred for additional 16 h. The organic layer is separated, dried and evaporated to dryness. Flash chromatography (silica, eluent ethyl acetate/cyclohexane 1:1, containing 0.5 % of 25 % aqueous ammonia) affords (10 mg, 5%) of the product as white solid. MS: m/e= 380 (M*).
Example 67 5-Methyl-thiophene-2-carboxyuc acid (4,5-dimemoxy-berm3truazol-2-ylVamide
2-Ammo^,5-dimethoxybanzothiazole (1.1 g, 5.3 mmol) and N,N.dimemylaminopyridine (47 mg, 0.37 mmol) are dissolved in pyridine (17 ml) and slowly treated with 5-methyl-thiophene-2-carbonyl chloride (1.5 g, 9.0 mmol). After 48 h at ambient temperature, the solution is evaporated to drynes. Hash chromatography (silica, eluent diethyl ether/cyclohexane 2:1) affords the product (618 mg, 35 %) as light yeHow solid.
Example 68
5-MemvI-tIiiophene-2-carboxyIic acid (4-cUoro-bm7nthia7ol-2-yD-amide
2-Amino-4-chlorobenzothiazol (92 mg, 0.50 mmol) is dissolved in dichloromethane (10 ml) and treated with pyridine (0.060 ml, 0.75 mmol) and 5-merayl-thiophene-2-carbonyl chloride (97 mg, 0.60 mmol). The reaction mixture is stirred at ambient temperature for 18 h and then evaporated to dryness. The residue is redissolved in ethyl acetate and water, the phases are separated and the organic layer extracted with brine. After dryin with sodium silfate, the solvent is removed in vacuo Flash chromatography on silica (eluent ethyl acetate/cyclohexane 1:4 affords the product as white solid.(88 mg, 57 %). MS: m/e= 308
Example 69
S-Meravl-thiophene-2-carboxya"c acid f7-broroo-4-me&oxy-benzothi37"1-2-T^-amidg
2-Amino--7-bromo-4-methoxybenzothia2ol (2.33 g, 9 mmol) is dissolved in dichloromethane (100 ml) and at 0 °C treated with pyridine (2.2 ml, 27 mmol) and 5-methyl-thiophene-2-carbonyl chloride (2.2 g, 13.5 mmol). The reaction mixture is allowed to warm to room temperature and after stirring for additional 18 h quenched with water (100 ml). After separation of the phases, the aqueous phases are extracted twice with ethyl acetate. The f"ir4*"i>*^^rgHiKlay«roaf*"titf*" yflshpri M"*h Win?! ^vi*^ ;HI^ ^g^pontM *n

dryness. Flash chromatography on silica (eluent ethyl acetate/cyclohexane 1:1 to 4:1) and final recrystallization from ethyl acetate affords the product as off-white solid. (34 mg, 69%). MS: m/e= 384 (M*).
Example 70
S-Methvl-t-hinphene-2-carboxyIic acid f4-fluoro-ben2othiazol-2-^")-amide
2-Amino-4-flourobenzothia2ol (84 mg, 0.50 mmol) is dissolved in pyridine (3 ml) and treated with 4-dimethylaminopyridine (1 mg) and 5-methyl-thiophene-2-carbonyl chloride (161 mg, 1.0 mmol). After stirring for 1 h at ambient temperature, the reaction mixture was evaporated to dryness. Hash chromatography on silica (eluent diethyl ether/cyclohexane 1:1 containing 0.5 % of 25 % aqueous ammonia) and final recrystallization from ethyl acetate affords the product as off-white soIid,(34 mg, 69 %). MS: m/e= 292 (M*).
Example 71 5-Methvl-thiophene-2-carboxviic acid (4-trifluoromethoxy-benzothiazol-2-y1)-aniifip
2-anmio-4-triflouromethoxybenzothiazol (70 mg, 0.30 mmol) is dissolved in pyridine (3 ml) and treated with 4-dhnemylarrdnopyridine (1 mg) and 5-methyl-thiophene-2-carbonyi chloride (96 mg, 0.60 mmol). After stirring for 4 h at ambient temperature, the reaction mixture was evaporated to dryness. Flash chromatography on silica (eluent ethyl acetate/cyclohexane 1:2) affords the product as white solid. (42 mg, 39 % yield). MS: m/e= 358 (M+).
Following the general method of example I, the compounds of examples 72 to 75 were prepared
Example 72
5-Methyl-tbinp>iene-2-carboxvIic acid (4-methoxv-7-morpholin-4-vl-berizothiazol-2-vl)-amide
Using 5-methyl-thiophene-2-carbonyl chloride and 2-amino-4-raethoxy-7-morpholin-4-yl-benzofhiazol die tide compound was obtained as a yellow solid in 97 % yield. MS: m/e= 390 (M+ET).
Example 73
6-Hvdroxy-pyriHinp-7.-rarboxv1ic acid f4-methoxy-ben7-nthia7^1-2-v1)-amidp

Using 2-Amino-4-methoiybenzothia2ole (450 mg, 2.5 mmol) and 6-hydroSypicolinic acid chloride (1.5 g, 10 mmol) the tide compound was obtained as a beige powder in 5 % yield. MS: m/e= 301 (Ivf).
Example 74 5-Meth^-thinphpne-2-carbr)xylic acid (7-benzyioxy-4-memoxy-ben2otbia7nl-^-Y^)~aTT1^""
Using 5-memyl-thiophene-2-carboxyhc acid chloride the title compound was obtained as an off-white solid (51 % yield). M.p.: 228-230 °C.
FoUowingihe general method of example 1, the compound of example 75 was prepared
Example 75
6-Chloro-N-f4-memoxv-7-phenTd-ben2X>miazol-2-yl)-nicotinamide
Using 6-chloro-nicotinyl chloride the title compound was obtained as a light yellow amorphous solid (79 % yield), MS: m/e=395.1 (M*).
Example 76
N-(4-Methoyy-7-phenyl-beiiznthia7oI-2-yl)-6-pyrrolidin- 1-yl-n ientinamiHg
To a solution of 6-chloro-N-(4-memoxy-7-phenyl-beiizothiazol-2-yl)-nicorinamide (297 mg, 0.75 mmol) in dioxane (10 ml) was added pyrrolidine (265 mg, 3.7 mmol, 5 eq.) and the mixture stirred at 100 °C for 2 h. After cooling the solvent was evaporated and the residue suspended in methanol (20 ml) at r.L, the solid was then filtered, washed with methanol and finally dried under vacuum (0.05 mmHg, 60 °C) to obtain die title compound as a white solid (230 mg, 71 % yield), MS: m/e=431.4 (M+H1").
Following the general method of example 76, the compounds of examples 77 to 80 were prepared
Example 77
3,4,5,6-TetrahYdro-2H-ro"1bipvridinvl-5"-carboxvlic acid (4-methoxv-7-phe^yIz benzotiiia7.nl -2-vTl-amiHe
Using piperidine the title compound was obtained as a light brown solid (59 % yield), MS: m/e=445.3 (M+H*).

Example 78
N-(4-Mdfaoxv-7-phenyl-benzothia2ol-2-yl)^morphoIm-4-Yl-nicotinainide
Using morpholine the title compound was obtained as a white solid (82 % yield), MS: m/e=447.2 (M+H*).
Example 79
N-(4-Methoxv-7-phenyl-benzothiazol-2-vl")-6- f 4-methyl-pip Using N-methyrpiperazine the title compound was obtained as a light brown solid (52 % yield), MS: m/e=460.4 (M+H*).
Example 80
N-f4-MethcCT-7-phenyl-benzothiazol-2-Yl)-6-thiomo^ hydrochloride salt (1:1)
Using thiomorpholine the free base of the title compound was obtained, which was then conveted to the hydrochloride salt by addition of 5N HCl/EtOH, affording the title compound as a white solid (78 % yield), MS: m/e=463.1 (M+H*).
Example 81
N-(4-Metiioxy-7-phenyl-ben20thia2ol-2-yl)^-fl-oxo-ll4-tMomorpholm-4-yi"l-nirntinaTTude hydrochloride salt (1:1)
To a solution of N-(4-melhoxy-7-phenyl-benzothia2ol-2-7l)-6-tMomorpholin-4-yl-nicotinamide hydrochloride salt (250 mg, 0.54 mmol) in chloroform (12 ml) was added 3-phenyl-2-(phenylsulfonyl)oxazmdine (211 mg, 0.81 mmol) and the mixture stirred at r.t for 2 hr. After evaporation of the solvent, the residue was suspended in CH2Q21 ultrasonnicated, then the precipitate was filtered oft washed with CH2G2, followed by ether and finally dried under vacuum (0.05 mmHg, 60 °C) to obtain the title compound as a light yellow solid (240 mg., 86 % yield), MS: mie=4Z92 (M+H*).
Example 82 4-Bromome1hvi-N-f4-memoxv-7-phenvl-beri2othia2o1-^-Yl)-hpn7aTTiide
To a solution of 4-bromomethyl-benzoic acid (5.45 g, 253 mmol) in toluene (60 ml) was aH^H *hi""yi "■hi"""** (18.25 ml, 25.3 mmol) and the mixture stirred at 80 °C for 16 h. The toluene and excess thionyl chloirde were then evaporated in vacuo and replaced with

THF (100 ml). To this solution was added 2-ammo-4-methoxy-7-phenyl-beiizotbiazole (5 g, 19.5 mmol), triethyiamhie (4.1 ml, 29.2 mmol) and DMAP (238 mg, 2 mmol) as catalyst, then the mixture stirred at 65 °C for 4 h. After cooling the reaction mixture was partitioned between 10% aq. Na2C03 (200 ml) and EtOAc (100 ml), the aqueous phase was extracte further with EtOAc/THF (1:1) (150 ml), then the combined organic phases were washed with satd. aq. NaCl (100 ml), dried (Na2SO*), filtered and evaporated in vacuo. The residue was then chromatographed over Si02 (Merck 230-400 mesh) eluting with a gradient of O^CyEtOAc (100 % CH2Q2 to 1:1), the product fractions were pooled and evaporated in vacuo to affords the title compound as a pale yellow solid (4.9 g, 55 % yield), MS: m/e=452.0 (M*).
Example 83
N-(4-Methoxy-7-phenvl-beiizothiazol-2-yl)-47pyrroUdm-l-ylmemyl-berizarnide hydrochloride salt (1:1)
To a solution of 4-fonnyl-N-(4-methoxy-7-phenyl-ben2othiazol-2-yl)-ben2ainide (300 mg, 0.77 mmol) in THF (60 ml) was added pyrrolidine (82 mg, 1.16 mmol), acetic acid (70 mg, 1.16 mmol) and NaBFJ(OAc)3 (246 mg, 1.16 mmol). This mixture was stirred for 16 h at r.L, then 5 % NaHCOs (30 ml) was added with vigorous stirring and the mixture extracted twice with EtOAc (50 ml). The organic phases were washed with saturates NaCl solution then dried, filtered and evaporated to afford the crude product which was converted to its hydrochloride salt and purified by reversed phase preparative HPLC using a Nucleosil (Machery-Nagel) N-protected column (20 x50 mm) and an MeCN/water (0.1 % TFA) gradient After pooling and evaporation of the product fractions the title compound was obtained as a white solid (217 mg, 59 % yield), MS: m/e=444.4 (M+H1").
Following the general method of example 83, die compounds of examples 84 to 89 were prepared
Example 84
N-f4-Memoxy-7-phenyl-hfmzothiazol-2-yl)-4-pipm hydrochloride salt (1:1)
Using piperidine the title compound was obtained as a light yellow solid (78 % yield), MS: m/e=458.4 (M+rT).

Example 85
N-(4-Methoxy-7-phenyi-bpn 7nt>iiazol-2-yn-4-niorpholin-4-,\dmethy1-^wiMmi da hydrochloride salt (1:1)
Using morpholine the title compound was obtained as a light yellow solid (23 % yield), MS:m/c=460.5(M+Ht).
Example 86
4-Diethvlammomemvl-N-f4-mei^oxv-7-phenvi-benzotiu^zol-2-^)-beii2amide hydrochloride (1:1)
Using diethylamine the title compound was obtained as a white solid (39 % yield), MS: m/e=446.3 (M+H+).
Example 87
N-(4-Methoxy-7-phenvl-bfin2otl]iazol-2-yi)^r(me& methyl]-benzamide hydrochloride salt (1:2)
Using 3-(memykminomefliyl)-pyridine the title compound was obtained as a Iigth yellow solid (15 % yield), MS: m/e=495.2 (M+If).
Example 88
N- i 4-Methoxv-7-phen,yI-beny.nfhia7r)l-2-yD-4-(4-meth"yl-piperazin-1 -ylmethyi)-benzamide hydrochloride salt f 1:2)
Using N-methyl-piperazine the title compound was obtained as a white solid (21 % yield), MS: m/e=473.3 (M+fT).
Example 89
4r-Pimethylaminome&yl-Kf-(4-rBellioxy-7-phenvi-benznthia7o1-?.-y1)-hpn7aiTi^Hf-hydrochloride salt (1:1)
Using dimediyiamine hydrochloride the title compound was obtained as a light yeflow solid (21 % yield), MS: m/e=418.3 (M+H*).

Example 90
4-Kf hylaTnin ometfavI-N-("4-methoxy-7-phenvl-benzothia2ol-2-vl 1-benzamide hydrochloride salt f 1:1)
To a solution of 4-bromomemyl-N-(4-methox7-7-phenyl-benzotiiiazol-2-yi)-benzamide (300 nig, 0.66 mmol) in THF (2 ml) was added ethylamine (2N in THF) (3 ml, 6.6 mmol) and the mixture stirred at 20 °C for 18 h. The reaction mixture was then evaporated to dryness and the residue treated with an excess of 5N HO/EtOH (3 ml), the ethanol was then evporated and the residue dissolved in DMSO and then subjected to preparative reversed phase HPLC purification using a C18 ODS-AQ column (20x50 mm), eluting with a gradient of MeCN/water (0.1% TFA). The product fractions were pooled and evaporated to afford the title compound as a light yellow solid (238 mg, 79 % yield), MS: m/e=418-3 (M+H+).
Following the general method of example 90, the compounds of examples 91 to 126 were prepared
Example 91
4-rf2-Memoxy-emv1amino)-memYl1-N-(4-methoxy-7-pheriYl-benzot>iia7j>l-2-v1)-benzamide hydrochloride salt (1:11
Using 2-metboxyethylarnine in dioxane at 90 °C the tide compound was obtained as a light yellow solid (.66 % yield), MS: m/e=448.3 (M+H+).
Example 92
4-[(2-Hydroxy-ethvlaminn1-memYl1-N-f4-methoxv-7-phenYl-benzolhiazol-2-yl1-benzamide hydrochloride salt (1:11
Using ethanolamine in dioxane at 90 °C the title compound was obtained as a light yellow solid (68 % yield), MS: m/e=434.4 (M+H*).
Example 93 4-(Benzykmino-methyl1-N- (4-methoxy-7-phenyI-ben7othiazol-2--yl )-hpn?ami cfc hydrochloride sart i1:\1
Using benzylamine in dioxane at 90 °C the title compound was obtained as a white solid (50 % yield), MSi m/e==48Q3 (M+lT)-

Example 94
4-[fBenzyi-methyl-aromoUmethyll-N-(,4-memoxv-7-phenyl-ben7.othia7ol-2--yl)-bertzamide hydrochloride salt d:11
Using N-methyl-benzylamine in dioxane at 90 "C the title compound was obtained as a white solid (74 % yield), MS: m/e=494.3 (M+lT).
Example 95
4- f f 3-Imidazol- 1-yl-prnpvl amino ,)-methyI1 -N-(4-memoxy-7-phenvl-beiizothiazol-2-yI1-benzamide hydrochloride salt f 1:21
Using l-(3-arninopropyl J-imidazole in dioxane at 90 °C the title compound was obtained as a pale yellow solid (58 % yield), MS: m/e=498.2 (M+H*).
Example 96
N-f4-Me&oxv-7-phenvl-ben2othiazol-2-yl)-4-Ufpyric^ benzamide hydrochloride salt (1:21
Using 4-(aminomethyl)-pyridine in dioxane at 90 °C the title compound was obtained as a beige solid (33 % yield), MS: m/e=481.2 (M+H+).
Example 97
4-{f(2-Memoxy-emvI1-meiiivl-amino1-me1h^ yl)-ben7flmTHp hydrochloride salt (1:1)
Using N-(2-memoxyethyl)-methylarnine in dioxane at 90 °C the title compound was obtained as a light yellow solid (73 % yield), MS: m/e=462.3 (M+H*).
Example 98 4- (1.1 -Dioxo^-tbiomoroho1in-4-ylme&y0-N-(4-mem^ benzamide hydrocblorde salt ("1:11
To a solution of N-(4-methoxy-7-phenyl-ben^othiazol-2-yl)-4-miomorpholm-4-yUiiethyl-benzamide (350 mg, 0.73 mmol) in CH2C12 (10 ml) was added 3-phenyl-2-(phenylsuifonyl) oxaziridine (288 mg, 1.1 mmol) and the mixture stirred for 2 h at r.L The reaction mixture was then evaporated to drynesss, the residue suspended in ether, and the solid filtered off and washed with ether followed by acetone. This solid was dissolved in methanol (10 ml) and treated with 5N HQ/MeOH for 1 h at rx, the resulting precipitate

was filtered off, washed with methanol and finally dried under vacuum (0.05 mmHg, 60 °C) to afford the title compound as a white solid (270 mg, 68 % yield), MS: m/e=508.3
(M+H+).
Example 99
N- (4-M^o^-7-phen?l-henzothiazol-2-^)^thiomorphohn-4-vlTTi et>iyl-b Using thiomorpholine in dioxane at 90 "C the title compound was obtained as a yellow solid (68 % yield), MS: m/e=476.1 (M+rf).
Example 100
A-TmiHarol-1 -ylniethyl-N-(4-melhoxy-7-phen^-benzothia7n1-2"yI")-benzanTide hydrochloride salt (1:1)
Using imidazole in DMF at 90 °C the title compound was obtained as a pale yellow solid (92 % yield), MS: m/e=441.3 (M+FT).
Example 101
4-(2-Hvdroxymethyl-imidazol- l-ybnethyD-rj"- (4-methoxy-7-phenyi-benzothiazol-2-ylV benzamide
Using 2-hydroxymethyl-imidazole in DMF at 90 °C the title compound was obtained as a pale yellow solid (16 % yield), MS: m/e=471.1 (M+H*).
Example 102
N-f 4-Methoxy-7-pheny1-bpn7otniazol-2-yD-4- (2-methvli-mifla7y.l-l -yimethyll-benzamide
Using 2-methyl-imidazole in DMF at 90 °C the title compound was obtained as a white solid (79 % yield), MS: m/e=455.5 (M+Ff).
Example 103
4- (4,5-Dir"^tbyl -iirndazol-1-ylmethvl) -N-f 4-memo:gy-7-phenyl-ben^OthiaZol-2-y^")-hpT]7.armHp
Using 4,5-dimethyl-imidazole in DMF at 90 °C the title compound was obtained as a pale yellow solkL (67 % yidd)TMSim/e=469.2 (M+HT)-

Example 104
N- (4-Methoxv-7-phenyl-ben2Qihiazol-2-yl"l-4-pipera2dn--1 -vimethvl-benzamide hydrochloride salt f 1:2)
Using 1-tert-butoxycarbonyl-pjperazine in dioxane at 90 °C the title compound was obtained as a pale yellow solid (80 % yield), MS: m/e=459.5 (M+H*).
Example 105
4-AHvlammomethyl"N-(4-methoxy-7-phenyl-beiH;otIn^zol-2-vl)-benzamide hydrochloride salt f 1:1)
Using allylamine in dioxane at 90 °C the tide compound was obtained as a pale yellow solid (65 % yield), MS: m/e=430.5 (M+lT).
Example 106
H-(4-Metfaoxv-7-phenyl-benzotHazol-2-yl)-4-propyTaminnmemyl-benzar]n^e hydrochloride salt (1:1.)
Using propylamine in dioxane at 90 °C the tide compoimd was obtained as a pale yellow solid (63 % yield), MS: m/e=432.4 (M+W).
Example 107
N-(4-Metho:xy-7-phenYl-beiizothiazol-2-yl^ bpny^TTuMe hydrochloride salt (1:2)
Using 3-(aminomemyl)-pyridine ia THF at 65 °C the tide compound was obtained as a pale yellow solid (28 % yield), MS: m/e=481.3 (M+H+).
Example 108
4-f4-Hyd^oxy-piperiHin-1-y1.aelhyl)-N- Using 4-hydioxy-pq>eridine in THF at 65 "C the title compound was obtained as a white solid (61 % yield), MS: m/e=474.3 (M+H*).

Example 109
4- (3( S)-Hydroxy-pyirolidin- l-vimethvD-N-f 4-metnoxv-7-phenvI-benzothiazol-2-yl)-benzamide hydrochloride salt (1:1)
Using (S)-3-hydroxy-pyrrob"dine in THF at 65 °C the title compound was obtained as a white solid (74 % yield), MS: m/e=460.3 (M+H""").
Example 110
4- T1,41 Diazepan-1 -yunethyl-N-f 4-methoxy- 7-phenvl-benzothiazol-2-yl)-benzamide hydrochloride salt f1:2)
Using tert-butyl-l-homopiperazine carboxyiate in THF at 65 "C the title compound was obtained as a light yellow solid (87 % yield), MS: m/e=473.2 (M+H*).
Example 111
4-f 3 ( R)-Dim ptbyl amfno-pyrrolidin- 1-vlmethyl) -N- f 4-methoxv-7-phenyi-benzothiazol-2-yl)-benzamide hydrochloride salt (1:2)
Using (3R)-(+)-3-dimethylamino-pyrolidine in THF at 65 °C the title compound was obtained as a light brown solid (51 % yield), MS: m/e=487.3 (M+H*).
Example 112
N-f 4-Methoxy-7-phenyI-benzothiazol-2-vD-4-1 (2-morpholm-4--^-ethv1amino)-methvl ] -benzamide hydrochloride salt (1:2)
Using 4-(2-aminoethyl)-morpholine in THF at 65 °C the title compound was obtained as a light yellow solid (44 % yield), MS: m/e=503.3 (M+H*).
Example 113
N-(4-Methoxv-7-phenvi-bfflzothiazol-2-yl)^r(2^ benzamide hydrochloride salt (1:2)
Using N-(2-aminoethyl)-pyrrolidme in THF at 65 °C the title compound was obtained as a light yellow solid (37 % yield), MS: m/e=487.3 (M+H*).

Example 114
N-(4-MethoxY-7-phenyI4ienzothiazoI-2-vD^rf2-piperi bemamide hydrochloride salt {1:2)
Using N-(2-aminoetiayl)-piperidinee in THF at 65 °C the tide compound was obtained as a ! light yellow solid (50 % yield), MS: m/e=501.3 (M+H*).
Example 115
4-Cvdobutykmmomelhyl^N-f4~memoxv-7-phenyl-ben7^thia7ol-2-yl")-bf,n7jm;Hp. hydrochloride salt (1:1)
Using cyclobutyiamine in THF at 65 °C the title compoimd was obtained as a white solid i (68 % yield), MS: m/e=444.3 (M+lT).
Example 116
4-Cydopentyiammomediyl-N-l"4-methoxy~7-phenyl-benzofliiazol-2-vl 1 -bgn7.amiH p hydrochloride salt f 1:1)
Using cyclopentylamine in THF at 65 °C the title compound was obtained as a light biown solid (46 % yield), MS: m/e=458.4 (M+H*).
Example 117
4-{[(Furan-2-ylmemyl)-aipmo1-memvU-N-(4^ benzaroide hydrochloride salt (1:1)
Using 2-(aminomediyl)-furan in THF at 65 °C the title compound was obtained as a beige solid (57 % yield), MS: m/e=470.2 (M+H*).
Example 118
N-(4-Methoxr-7-phmYl-hqm>ihiazol-2-Yl)-4-W benzamide hydrochloride salt (1:1)
Using 2-(aminomethyi)-djiophene in THF at 65 °C the title compound was obtained as a light yellow solid (60 % yield), MS: m/e=486.3 (M+H*).
Example 119

4-Diprop^aininomediyl-N-f4-methoxv-7-phen^-benzothiazol-2-^"l-benzamide hydrochloride salt (1:1)
Using dipropyiamine in THF at 65 °C the tide compound was obtained as a white solid (64 % yield), MS: m/e=474.3 (M+H*).
Example 120
N-f4-MethoCT-7-phenyi-benzodiiazoI-2-yl)^U methyil-"henzamide hydrochloride salt (1:21
Using 2-[(2-(meth)damino)ethyi]-pyridine in THF at 65 °C the tide compound was obtained as a beige solid (46 % yield), MS: m/e=509.3 (M+H*).
Example 121
4-AmmomeraYl-N-f4-metfao:^-7-phenvi-benzothiazol^ salt f 1:1)
Using ammonia (7N in MeOH) in THF at 20 °C the tide compound was obtained (after 4 days) as a white solid (34 % yield), MS: m/e=3891 (M*).
Example 122
4-1 (CyclopTQP^methvI-amino)-memyl1 -N-(4-memoxy-7-phenyi-ben7.ntinazol-2-vl)-henramide hydrochloride salt (1:1)
Using aminomethyl-cyclopropane in dioxane at 90 °C the title compound was obtained as a light yellow solid (69 % yield), MS: m/e=444.3 (M+H+).
Example 123
N-(4-MethoxY-7-phenvi-beiizothiazol-2-vl)-^ benzamide hydrochlorde salt (1:2)
Using 2-(methyldiio)-ediylamine in THF at 65 °C the title compound was obtained as a light ydlow solid (74 % yield), MS: m/e=464.2 (M+H1").
Example 124
N-(4-Memoxv-7-phenvl-benzotniazol-2-yl)-4-tniazoBdm^ bvrirorfflordeaak(l:l)

Using thiazolidine in THF at 65 °C the title compound was obtained as a white solid (48 % yield), MS: m/e=462.2 (M+H*).
Example 125
4-(3(S)-Dimrthylarnmo^pvrroKdm-l-yimethv^^ yQ-benzamide hvdrochiorde salt (la)
Using (3S)-(-)-3-(dmiemylaniino)-pyrroIidine in THF at 65 °C the title compound was obtained as a light brown solid (56 % yield), MS: m/e=4S7.3 (M+H*).
Example 126
4-ff2-DJinrthy1aTniiio-ethy]aminoymrthvl1-N-f4^ benzamide hydrochloride salt (1:2)
Using 2-{dmiethylamino)-ethylamine in THF at 65 °C the title compound was obtained as a light yellow solid (32 % yield), MS: m/e=461.3 (M+ H*).
Preparation of the 4-0R1R2-ammo)-N-(4-methoxy-7-ai7l-ben2othiazol-2-yl)-benzainides:
General Procedure G The appropriate 2-amino--7-aryl-4-methoxy-benzothiazol is converted with 4-(chloromethyl)ben2oyl chloride using the general method of example 1. The product is then converted neat with the appropriate amine (10 equivalents) at 100 "C for 24 hours. The reaction mixture is then dissolved in ethyl acetate, extracted with water and brine, dried and evaporated in vacuo. Flash chromatography (silica, eluent dichloromethane containing 1.2 to 2.4 % methanol) affords the product in about 50 % yield.
Example 127 4-Qoromethyl-N-("4-me&oxy-7-niorp]M^
and 2-ammo-4-methoxy-7-morphoIin-4-yi-benzomiazol (1-0 g, 3.8 mmol), 4-(chloromethyi) benzoyl chloride (810 mg, 4.2 mmol) and pyridine (036 ml, 4.5 mmol) are reacted in dichloromethane (20 ml) for 18 h. The reaction is quenched with water (25 ml) and brought to pH 8.0 with sodium carbonate. The mixture is extracted with dichloromethane and the combined organic layers are dried and evapoarted to dryness. Flash chromatography (silica, eluent methylene chloride containing 2.5 % methanol) affords the product as white crystalls in 54 % yield. MS: m/e= 418 (M+H*").

FoJhwingthe general method the compounds of examples 128 to 132 were prepared
Example 128
4-f4-HYdroy^-piperidm-l-vlmemyl)-N-(4-memoxy-7-morpholm^-yl-benzothiazol-2-vlVbenzamide
Ojnverdonof4KJoromethyi-N-(4-memoxy-7-morpholm^yi-benzothia2»l-2-yi)-benzamide (&4 mg, 0.20 mmol) -with 4-b-ydroxypipeia2m (200 mg, 2.0 mmol) using lie general procedure C affords the product as white solid in 73% yield. MS: m/e= 483
(M+H+).
Example 129
4-S [ (2-Methoxv-etfaylVmethvl-amino] -meth"vi}-N-(4-methoxv-7-morpholin-4-yl-
benzothiazol-2-vl")-beiizamide
Conversion of 4^oromethyl-N-(4-methoxy-7-morpholm-4-yl-benzothiazol-2-yi)-
benzamide (84 mg, 0.20 mmol) with N-(2-memoxyemyl)-memylarmn (178 mg, 2.0 mmol)
using the general procedure C affords the product as white solid in 55% yield. MS: m/e=
471 (M+H*).
Example 130
4~f f (2-Hvdroxy-ethyI)-methyi-amino ] -methyl ?-N-(4-metnoxy- 7-morphoiin-4-yi-ben2othiazol-2-yl)-benzamide
3,4-Dimethoxy-benzoic add 2-{[4-(4-memoxy-7-morpholm-4-yl-benzothiazol-2-yl carbamoyl)- benzyl] -methyl-amino}-ethyl ester (63 mg, 0.10 mmol) are heated in aqueous sodium hydroxide (1M, 0.5 ml) and ethanol (2 ml) to 100 °C for 30 min The mixture is diluted with water and extracted twice with ethyl acetate. The combined organic layers are extracted with saturated aqueous sodium hydrogencarbonate, dried and evaporated to dryness. Flash chromatography (silica, eluent methylene chloride containing 5 % methanol) affords the product as white crystals in 48 % yield. MS: ra/e= 457 (M+H*).
Example 131
3,4-Dimethoxv-benzoic acid 2-{f4-(4-methoxv-7-morph,nli"-^-Yl-benzothiazol-2-yicarb^mr.yl)- hfri7yl|-methyl-a™"nol-ethyl ester
Q3nveraonof4-dorome1iiyl-N-(4-memoxy-7-morpholm-4-yI-benzothiazol-2-yl)-benzHnnVfe (84 nig; (K2fr rmnof^ with 3,4-£m.dthvxywiixoiC JCKT 2-merhyIaximio;-eth"yI

ester chlorohydrate (96 mg, 0.4 mmol) and N-ethyl diisopropyiarnine (0.14 ml, 0.80 mmol) using the general procedure C affords the product as light yellow solid in 57% yield. MS:m/e=621(M+lT).
Example 132 N-f 4-Memory-7-morphoIm-4-yl-berizothiazol-2-yi)-4-pipera2in-1 -ylmethyi-benzamide
Conversion of 4-doromemyl-N-(4-memoxy-7-morpholm-4-yl-benzothiazol-2-yl)-benzamide (84 mg» 0.20 mmol) with 1-BOC-piperazine (372 mg, 1.9 mmol) using the general procedure C and afterwards cleavage of the neat carbamate in trifluoroacetic acid (1 ml) followed by saturated aqueous sodium carbonate affords the product as colorless crystals in 72% yield. MS: m/e= 468 (M+H*).
Example 133 N-(7-Ben2^oxp-4-methoxv-benzothiazol-2-yl)-4-chloromeaSYl-hf?ny.arniH^
Following the general method of example 1 the title compound was obtained as a light yellow solid (70 % yield). MS (EI): me/e = 438 (M*).
Example 134
N- f 7-Benzvloxy-4-memoxy-hen7nthiazol-2-yl)-4~( ^-Himethylamino-pyrroUdm-1-vtmethyi)-^*"?an-nde hydrochloride
According to general procedure C the title compound was obtained as a light brown solid (86 % yieId)..M.p.: 195° C (dec).
Preparation of the 3^f7-arvi^methoxy-benzothiazol-2-yl)-l--R3-l-R General procedure D: The appropriate 2-arnino-7--aryi-4-methoxy-benzothiazol (1 part) and pyridine (1.2 equivalents) are dissolved in 40 parts tetrahydrofuran and treated with phosgene (20 % in toluene, 1 equivalent) at ambient temperature. After 60 min, the reaction mixture is concentrated to half the volume under reduced pressure and the appropriate amine (1.25 equivalents) and pyridine (1.1 equivalents) are added. After 15 min at ambient temperature, the reaction mixture is evaporated to dryness. The product is isolated by flash chromatography (silica, eluent dichloromethane containing 2.5 % methanol).

FoUowingthe general method the compounds of examples 135 to 137 were prepared
Example 135
Tbiomorpholine-4-cafboxylic acid f4-memoxy-7-morpholm-4-yl-benzotfaiato]-2-yl)-amide
Conversion of 2-andno-4-methoxy-7-morpholin-4-yl-ben2otbia2ol (100 mg, 0.377 mg) with phosgene (20 % in toluene, 0.2 ml) and thiomorpholine (0.045 ml, 0.47 mmol) using the genera] procedure D affords the product as white solid in 73 % yield. MS: m/e= 395 (M+H+).
Example 136 Morpholine-4-carboxylic acid (4-methoxy-7-morphoIm^-yl-benzothia2oI-2-viVamide
Conversion of 2-amino-4-methoxy-7-morpholin-4-yl-benzo&iazol (100 mg, 0.377 mg) with phosgene (20% in toluene, 0.2 ml) and morpholine (0.041 ml, 0.47 mmol) using the general procedure D affords the product as white solid in 25 % yield. MS: m/e= 379 Example 137
3- f 4-Methoxy-7-mor^holin-4-yl-benzothiazoi-2-vlV 1-methyl-1 -(6-methyl-pvridin-3-yimethvD-urea
Conversion of 2-amino^-methoxy-7-morpholm^yl-benzothiazol (100 mg, 0.377 mg) with phosgene (20 % in toluene, 0.2 ml) and memyl-(6-merhyl-pyridm-3-ylmemyl)-aniine (0.064 ml, 0.47 mmol) using the general procedure D affords the product as white solid in 25 % yield. MS: m/e= 429 (M+H+).
Example 138
l-Furan-2-yi-memvl"3-(4-me^oxy"benzothiazol-2-,vi")-urea
To a solution of (4-Methoxy-benzothia2ol-2-yl)-carbamic acid tert-butyl ester (80 mg> 0.29 mmol) in dioxane (2 ml) was addded furfiirylamine (55 mg, 0.57 mmol) and the mixture heated to 100 °C for 20 h. The reaction mixture was then evaporated to dryness and the residue recrystallised from ether/nHexane to afford the title compound as a beige solid (80 mg, 92% yield), MS: m/e=303 (M*).

Following the general method of example 138, the compounds of examples 139 to 163 were prepared
Example 139 1 -Furan-2-vi-methyl-3- (-4-methoxy-7-phen^-benzothiazol-2-yl)-urea
* Using (4-Methoxy-benzothiazol-2-yl)--carbamic acid tert-butyl ester and forfiirylamine the title compound was obtained as abeige solid (66 % yield), MS: m/e=380.3 (M+H+).
Example 140 l-(4-Me&oxy-7-phen^d-benzo1faiazol-2^)-3-thiophen-2-yl-methvl-urea
Using (4-methoxy-7-phenyl-ben2oyhiazol-2-yl)-carbamic acid tert-butyl ester and " tIriophene-2-methyiamine the title compound was obtained as a beige solid (62 % yield), MS: m/e=396.3 (M+JT).
Example 141
l-(4-Memoxy-7-phenyl-ben20tlmzol-2-yl)-3-pvridin--2-vl-methyl-urea
Using (4-methoxy-7-phenyl-benzoyhia2ol-2-yl)-carbamic acid tert-butyl ester and 2-(aminomethyl)-pyridine the tide compoundwas obtained as a beige solid (18 % yield) following purification using reversed-phase preparative HPLC C18 ODS-AQ, with an MeCN/ water gradient, MS: m/e=391.2 (M+H+).
Example 142 l-f4-Methoxv-7-phenyl-beri2othiazoI-2-yl)-3-pyrTHin-3-^mf-thYl-i]rea
Using (4-methoxy-7-phenyl-benzoyhiazol-2-yl)-carbamic acid tert-butyl ester and 3-(aminomethyl)-pyridine the tide compound was obtained as abeige solid (18 % yield) following purification using reversed-phase preparatie HPLC, CI 8 ODS-AQ, with a water/acetonitrile gradient, MS: m/e=391.2 (M+Ef).
Example 143
l-(4-Memo:xT-7-phenyl-berizo1hiazol-2-yl)-3-pTO
Using (4-metnoxy-7-phenyl-ben2»yhiazol-2-yl)-carbamic acid tert-butyl ester and 4-(aminomethyl)-pyridine the tide compound was obtained as a beige solid (52 % yield), MS:m/e=391^(M+lT).

Example 144
3-f4-Memo:%y-7-phenyl-benzolliiazol-2-vl)-l-meth^
Using (4-methoxy-7-phenyl-ben2oyhia2ol-2-yl)-carbamic add tert-butyl ester and 3-(methylaniinomethyl)-pyridine the title compound was obtained as a bdge solid (23 % yield), MS: m/e=405.4 (M+H*).
Example 145
1 - C4-Methoxv-7-phemyl>benzothiazol-2-vl)--3-phenetbyl-urea
Using (4-methoxy-7-phenyl-ben2oyhiazol-2-yl)-carbainic add tert-butyl ester and pbenethylamine the title compound was obtained as a beige solid (77 % yield), MS: m/e=404.5 (M+H*).
Example 146
l"f4-Methoxy-7-phenyl-benzotbia2ol"2-yl")-3-(3-phenyl-propyl)-urea
Using (4-metboxy-7-phenyl-benzoyhiazol-2-yl)-carbamic add tert-butyl ester and 3-phenyl-propylamine the title compound was obtained as a beige solid (71 % yield), MS: m/e=4173 (M+H*).
Example 147 l-f4-Memoxy-ben^)-3-(4-metboxy-7-phenyl-benzothiazol-2-vl)-urea
Using (4-methoxy-7-pnenyl-benzoyhiazol-2-yl)-carbamic add tert-butyl ester and 4-methoxy-benzykmine the title compound was obtained as a beige solid (60 % yield), MS: m/e=420.3 (M+H*).
Example 148
3,4-Dihydro-lH-isoquinoline-2-carboxyiic add (4-metfaoxv-7-phenyl-ben2otbiazol-2-yl)-amide
Using (4-me1noxy-7-phenyl-benzoyhiazol-2-yl)-carbamic add tert-butyi ester and 1,23J4-tetrahydroisoquinoline die title compound was obtained as a beige solid (31 % yield) following purification using reverse-phase prep. HPLC, C18 ODS-AQ, with a water/acetonitrile gradient, MS: m/e=416.3 (M+H1").

Example 149 I - (2-Dunethviamino-ethyO-3-(4-methoxy-7-phenvi-benzothiazol-2-yi)-urea
Using (4-methoxy-7-phenyl-benzoymazo]-2-yl)-carbamic acid tert-butyl ester and 2-dimethylamino-ethylamine the title compound was obtained as a beige solid (67 % yield), MS:m/e=371.3(M+H+).
Example 150
1 - (2-Hvdjoxy-ethylV3-f 4-methoxy-7-phenylrbenzothiazol-2-yl)-urea
Using (4-methoxy-7-phenyi-benzoybiazol-2-yl)-caibamic acid tert-butyl ester and ethanolamine the title compound was obtained as a beige solid (35 % yield), MS: m/e=344.3 (M+H+).
Example 151 1 - (4-Methoxy-7-phenyl-benzothiazol-2-vI1-3-( 2-piperidin-l-yi-ethyH-urea
Using (4-methoxy-7-phenyl-benzoyhiazol-2-yi)-carbamic acid tert-butyl ester and l-(2-aminoethyl)-piperidme the title compound was obtained as a beige solid (67 % yield), MS: m/e=411.4(M+H+).
Example 152 l-f4-Me&oxv-7-phenyl-berizolhia2ol-2-ylV3-{2-morpbolm^vi-elfayiVurea
Using (4r-methoxy-7-phenyi-benzoyhiazol-2-yi)-carbarnic acid tert-butyl ester and 4-(2-ammoethyl)-morpholine the title compound was obtained as a beige solid (29 % yield), MS:m/e=413.4(M+rD.
Example 153
I- f 4-Methoxv- 7-phenvl-benzothia7.nI-3-vl )-3-f 2-pyridin-2-vi-ethyD-urea
Using (4-rnethoxy-7-phenyl-benzoyhiazol-2-yl)-carbamic acid tert-butyl ester and 2-(2-aminoethyl) -pyridine the title compound was obtained as a beige solid (88 % yield), MS: m/e=405.4 (M+H*).
Example 154
i-r^-Tmidazol-l-yl-propyl)-3-(4-Tnethoxv-7-phenyl-bfin7rttliia7nl-2-ylVurea hydrochloride salt (1:11

Using (4-methoxy-7-phenyl-ben2»yhiazol-2-yl)-caibamic acid tert-butyl ester and N-(3-aminopropyl)-iniidazole the free base was obtained which was was treated with 5N HCl/EtOH followed by crystallisation from methanol/ether to afford the titie compound as a beige solid (72 % yield), MS: m/e=408.3 (M+-H*).
Example 155
l-Ethrl-3-(4-memoxy-7-phenyl-benzothi^ hydrochloride salt f 1:1)
Using (4-methoxy-7-phenyl-benzoyhiazol-2-yl)-carbamic acid tert-butyl ester and4-(N-emylaminomethyl)-pyridine the free base was obtained which was was treated with 5N HCl/EtOH followed by crystallisation from acetonitrile to afford the titie compound as a white solid (64 % yield), MS: m/e=419.3 (M+H*).
Example 156
l-f2-Imid^oI-l-yl-emYl)-3-(4-memoxy-7-phenyl-benzothiazol-2-vl>-ureahydrocM salt f 1:1)
Using (4-methoxy-7-phenyi-ben2oyhia2ol-2-yl)-carbamic acid tert-butyl ester and N-(2-ammoemyl)-imidazole the free base was obtained which was was treated with 5N HCl/EtOH followed by crystallisation from a Example 157 Morpholine-4-carboxylic acid f4-methoxy-7-phenyl-benzothiazoI-2-yl)-aTnide
Using (4-methoxy-7-phenyl-benzoyhiazol-2-yl)-caibamic add tert-butyl ester and morpholine the the title compound was obtained as a white solid, following crystallisation from ether/ nHexane (67 % yield), MS: m/e=370.3 (M+rT)
Example 158 Thiomorpholine-4-carboxyUc acid (4-methoxy-7-phenyl-ben2otbiazol-2-vl")-amide
Using (4-methoxy-7-phenyl-benzoyhiazol-2-yl)-carbamic acid tert-butyl ester and thiomorpholine the the title compound was obtained as a white solid, following crystallisation from ether/nHexane (88 % yield), MS: m/e=386.2 (M+H*).

Example 159
1-Oxo-ll 4-diiomorphfi1inp-4-carboxvhc acid (4-methoxy-7-phenvl-benzothia2ol-2-yD-amide
To a solution of thiomorpholine-4-carboxylic acid (4-methoxy-7-phenyl-benzothiazol-2-yl)-amide (240 mg, 0.62 mmol) in CH2CI2 (10 ml) was added 3-phenyi-2-(phenylsulfonyl) oxaziridme (244 mg, 0.92 mmol) and the mixture stirred for 2 h at r.L The solvent was then reduced to ca. 2 ml and the mixture ultrasonnicated for 15 min. with addition of ether (10 ml). The solid precipitated was filtered off, then dried under vacuum (0.05 mmHg, 60 °C) to afford the tide compoundas a light yellow solid (90 % yield), MS: m/e=402.9 (M+if).
Example 160
!-[2-(lJ-IMoxo-ll6-tMomorpholm^vlVethvI1-3-f4-medioxy-7-pheiiyl-benzothiazol-2-yD-urea hydrochloride (1:1)
Using (4-meliioxy-7-phenyl-ben2oyhia2ol-2-yl)-carbaniic acid tert-butyl ester 2-(l,l-Dioxo-tmomorpholin-4-yl)-emyIainine the free base was obtained, which was converted to the hydrochloride salt by treatment with 5N HQ/EtOH followed by under vacuum (0.05 mmHg, 60 °C) to afford the title compound as a beige solid (87 % yield), MS: m/e=4612
(M+rT).
Example 161
3- f 4-Methoxy-7-phenyi-ben2othi azol-2-yIV 1 -methvl-l-(6-roedivl-pyridin-3-yI-memyl")-urea hydrochloride salt (1:2)
Using (4-methoxy-7-phenyl-benzoyhiazol-2-yl)-carbamic acid tert-butyl ester and metiiyl-(6-memyI-pyridm-3-ylmethyl)-amhie, the free base was obtained, which was converted to the hydrochloride salt by treatment with 5N HQ/EtOH followed by recrystallisation from acetonitrile then drying under vacuum (0.05 mmHg, 60 °C) to afford the tide compound as a white solid (61 % yield), MS: m/e=448.9 (M+H+).
Example 162
3-(4-Methoxv-7-phenyl-benzotbiazol-2-yl)-l -mefliyl-l-pyriHin -7-yl-methvl-urea hydrochloride salt (1:2)
Using (4-methoxy-7-phenyl-benzayhiazoI-2-yl)-carbamic acid tert-butyl ester and methyl-pyridin-2-yl-mediyl-amine, the free base was obtained, which was converted to the

hydrochloride salt by treatment with 5N HCl/EtOH followed by recrystaffisation from EtOH/ether then drying under vacuum (0.05 romHg, 60 °C) to afford the title compound as a white solid (70 % yield), MS: m/e=494.4 (M+H+).
Example 163
3-j4-Methoxy-7-phenyI-benzothiazol-2-yl) - l-methyl-1 -pvridin-4-vi-methvi-urea hydrochloride salt (1:2^
Using (4-methoxy-7-phenyl-berizoyhia2ol-2-yi)-carbamic acid tert-butyi ester methyi-pyridin-4-ylmethyl-arnine the free base was obtained, which was converted to the hydrochloride salt by treatment with 5N HCl/EtOH followed by recrvstaflisation from EtOH/ether then drying under vacuum (0.05 mmHg, 60 °C) to afford the title compound as a white solid (65 % yield), MS: m/e=480.3 (M+fcT).
Example 164
3-(4-Methoxv-7-phenyl-benzotliia2ol-2-vI)-l-met^^
To an ice cooled solution of 3-(4-memoxy~7-phenyl-benzotluazol-2-yl)-l-methyl-l-pyridin-3-yl-methyl-urea (405 mg, 1 mmol), in CH2CI2 was added 3-chloro-perbenzoicadd (MCPBA) (295 mg, 1.2 mmol) and the mixture stirred at 0 °C for Ih, followed by 1 h at r.t After this time the pale red reaction mixture was thoroughly washed with 5% NaHC03 solution (50 ml), and the aqueous phase was extracted with CH2G2 (2x 30 ml) then the combined extracts were dried with Na^CU, filtered and evaporated to affording a violet solid. This solid was then chromatographed over SiCh (Merck 230-400 mesh) during with a gradient of CH2a2/(2N NHj/MeOH) (97:3 to 9:1), to afford the tile compound as a light brown solid (260 mg, 62 % yield),MS". m/e=421.3 (M+H*)
Example 165 l-Benzvl-3-f4-methoxy-benzothiazol-2-vl)-urea
To a stirred solution of 2-amino-4-methoxy--ben2othiazole (180 mg, 1 mol) in THF (5 ml) was added benzylisocyanate (166 mg, 1.25 mmol) and the mixture heated to 60 °C for 3 h. After evaporation of the solvent, ether (5 ml) was added and the suspension ultra-sonnicated for 10 min with addition of nHexane (5 ml). This suspension was filtered and washed further with ether/nHexane (1:1) to afford the title compound, after drying under vacuum, as a white solid (220 mg, 70 % yield), MS: m/e=313 (M*).

Following the general method ofexample 165, the compound of example 166 was prepared
Example 166
l-Berizvl-S-f^metnoxy-y-phen^-berizothiazoI^-^Vurea
Using 2-ammo-4-memoxy-7-phenyi-benzothiazoIe the title compound was obtained as a white amorphous solid (92 % yield), MS: m/e=389 (M*)
Example 167 1 - f 4-Methoxy-7-phenvi-benzntliia7.pl -2-yl)-3-pyriHin-Vyl-thi nnrea
To a stirred solution of 2-arnmcK4-methoxy-7-phenyl-benzothiazole (80 mg, 0.3 mmol) in dioxane (3 ml) was added pyridine-3-isothiocyanate (64 mg, 0.47 mmol) and the mixture heated to 100 °C for 69 h. After cooling to r.t the resulting yellow suspension was filtered, washed with ether (5 ml) and dried under vacuum (0.05 mmHg, 50 °C, to afford the tide compound as a; light yellow solid (98 mg, 80 % yield), MS: m/e=393.1 (M+H+).
Example 168 l-Benzoyl-3-f4-methory-7-phenyl-ben2othmol-2-viVthiourea
To a suspension of 2-amino-4-methoxy-7-phenyI-benzothiazoIe (1.52 g, 6 mmol) in dioxane (60 ml) was added benzoyusothiocyanate (1.45 g, 8.9 mmol) and the mixture heated to 100 °C for 2 h, during which time the suspension dissolved. After cooling the solvent was removed and the solids suspended in hot acetonkrile (100 ml) and filtered while warm (50 °C). The solid collected was washed with acetonitrile (20 ml) then dried under vacuum (0.05 mmHg), at 60 °C. to afford the tide compound as z pale yellow amorphous solid (1.38 g, 55 % yield), MS: m/e=419.0 (it).
Example 169 (4-Methoxy-7-phenyl-benzothiazol-2--vl)-thiourea
To a solution of l-benzoyl-3-(4-memoxy-7-phenyl-ben2otiiiazol-2-yi)-thiQurea (13 g, 3.1 mmol) in methanol (20 ml)/THF (40 ml) was added NaOMe (250 mg, 4.6 mmol) and the mixture stirrd for 72 h at r.t. After evaporation of the solvents water (100 ml) was added with stirring followed by aceticacid (1 ml) which caused a solid to precipitate. This solid was collected and on a glass sinter, washed with water (100 ml), followed by EtOAc (30 ml) then finally cyciohexane (30 ml). After drying the tide compound was obtained as a white solid (850 mg, 87 % yield), MS: m/e=316.2 (M+JT).

Example 170
(4-Methoxy-beiizothiazol-2-yl)-iirea
Amixtureof2-anihio-4-methox7-ben2othiazole(330rag, 1.83 mmol) and urea (1.1 g, 1.83 mmol) were heated together for 1 h at 170 °C, with evolution of ammonia. After allowing to cool to r.t, water (10 ml) was added and the mixture was vigorously stirred. The solid was then filtered, washed, with water (10 ml) followed by ethanol (10 ml) and dried at 60 °C under vaccum (0.05 mmHg). The tide product was afforded as an off-white solid (300 mg, 73 % yield), MS: m/e= 223 (M+).
FoUowing the general method of example 170, the compounds of examples 171 to 173 were prepared
Example 171 f4-Memoxy-7-phenyl-benzothia20I-2-yI)-urea
Using 2-airuno-4-methoxy-7-phenyl-beazotbiazale the title compound was prepared as white solid (58 % yield), MS: m/e= 299 (M+). The preapration of this compound is decribed in the following patent literature; N-(Benzothiazol-2-yl)oxamic acid derivatives. W. Winter, M. Thiel, A. Roesch and O. H. WUhelms, German Patent, DE 2656468,1978.
Example 172 f4,6-Difluoro-bep7nthia7nl-2-yl1-urea
Using 2-ammo-4J6-difluoro-benzothiazole the title compound was prepared as a light yellow solid (42 % yield), MS: m/e= 229 (M+).
Example 173 (7-Isopropyi-4-methaxy-ben2Qtbiazol-2 -yD-urea
The title compound is described in the following patent literature and was prepared according to the procedure described therin; N-(Benzothiazol-2-yl)oxamic acid derivatives. W. Winter, M. Thiel, A. Roesch and O. H. Wilhelms, German Patent, DE 2656468,1978.
Example 174 (4-Methoxv-7-phenyl-bertzotbiazol-2-yl)-pyric%i-3-yhiiethvl-amine

WE CLAIM:
1. Novel benzothiazolc derivatives of formula
wherein
R1 is hydrogen, Ci.6-alkyl, Ci-s-alkoxy, benzyloxy, cycloalkyloxy, halogen, hydroxy oi tiifluoromethyloxy,
R3 is hydrogen, halogen, Q-e-alkyl or Cus-alkyloJcy;
R* is hydrogen, C^-alkyl, C3-s-aIkenyl, halogen, -C(O)- Q-e-alkyL -C(0)-halogen-Q. s-alkyJ, -CH(OH)-haIogen- Cu-alkyl, -C{0)0-Q^- alkyl, -NHC(O)- C].s-alkyi, -(CH2)n-OH, or is phenyl, which is optionally attached to the benzo group via the linker - (0)m-(CH2)a- and is optionally substituted by N(Rs)(R6), halogen or nitro, or is 2;,3-dihydrQ-lH-indolyl,a2epan-l-yl, [l,4]oxazepan-4-yI, oris a five or six rnembered aromatic or non aromatic heterocyde, which may be attached to the benzo group via the linker - (0)m-(CH2)„ or - N=C(CH3)-and is optionally substituted by one or two group(s) R7, wherein R7 is defined below; with the proviso that Rl, E.3 and R4 are not simultaneously hydrogen,

R7 is d.ralkyl, Ce-alkoxy, -C(O)^ Cs-alkj-l, -C(0)Q-ben2yl, -C(0)0- G-s-alkyl, - (CH2)nNR5R6, pyridinyl, optionally substituted by Ci-g-alkyl, or is -CH2N(R5)-C(0)0-Ci-e-aIkyl, -NH-C(phenyI}3, pyrrolidinyl, piperidinyl, morpholmyl or piperazinyl, optionally substituted by Ci.s-alkyl;
n is 0, 1,2, 3 or 4;
m is 0 Or I;
o is 0, 1,2, 3 or 4;
and their pharmaceutically acceptable salts,
2. Novel compounds of formula IA according to claim |
wherein
R1 is hydrogen, Q-e-alkyl, Q^-alimy, halogen, hydroxy or trifluoromethyioxy;
R3 is hydrogen, halogen, C2.6- alkyl or Ci^-alfcyloxy;
R4 is hydrogen, d.s-alkyi, halogen, -C(0)OH, -CfO)0- CM-alkyl, -NHC(0)-Ci-6-alkyl, -{CHJJQ-OH, or is phenyl, which is optionally attached to the benzo group via the linker - (0)m-(CH2)„- and is optionally substituted by N(RS)(R6), halogen or nitro; or is a five or six membered aromatic or non aromatic heterocycle, which is attached to the benzo group via the linker - (0)m-(CH2)n and is optionally substituted by Ci-s-alkyl, -C(0)0-benzyl or - NRSR6;
with the proviso that R1, RJ and R4 are not simultaneously hydrogen,
R" is
phenyl, substituted by -C(0)H, or by the following groups -(CH2)nOH with the exception of OH,

-(CH2)nN(RE)-(CH2)0- Ci.(r-aIkoxy,
-CCH2)nN(R5)-(CH2)D-cycloalkyl, -(CH3)nN(Rs)-(CH2)D-S- Q.s-alkyl, -(CH2)nN(R5)-(CH2)0-phenyI, -{CH2)„N(R5)-(CH2)0OH, -(CH2)nN(R5)-(CH2)0~0-CH(OH)-QH3(OCH3)2, -(CH2)nN(R5)-(CH2)0-O-C(O)-QH3(OCHs)2, -S(0)2-morpholin
or is phenyl, which is optionally substituted by
-(CKkJn-five to seven rnembered aromatic or non aromatic heterocycle, and wherein the heterocycle may farther substituted by hydroxy, -N(R5)(R6) or Q.s-alkyl;
X isOor S;
R5, R6are independently from each other hydrogen or Ci-j-aBcyl,
n is 0,1,2, 3 or 4;
m is 0 or 1;
o isO, 1,2, 3 or 4;
and their pharrnaceutically acceptable salts,
!. The compounds of formula 1A in accordance with claim 1, wherein R1 is methoxy, X is oxygenand R3 is hydrogen.
The compounds of formula IA in accordance with claim 3, wherein R" is phenyl, substituted by -CH2OH, -CH:NHCH2CH2OCH3, -eH2NHCHaCH2OH, -CH2NHCH2-pyridinyl, -CH2NH2, -CH2NHCH:CH:SCH3, -CH2N(CH3)CH3CH2SCH3) -CHjN(CH3)CH2CH;OCH3, -CH2N(CH2 CHj)CH2CH2OCH3, -CH2NHCH3, -CH2SCHjCH2N(CH3)2, -CH2OCH3, -CH2OCH2CH2OCHj or -CH:N(CH3)C(0)OCH3.
The compounds of formula IA in accordance with claim 4, which compounds are 4-hydroxymethyl-N- (4-methoxy-7-pheny!-benzathiazal-2-yl) -benzamide,

yi)-benzamide,
3H((2-m«hory-ethyI)-m«hyl-antiiio]-methyI}-N-(4-methoxy-7-inorpholiii-4-yl-
benzothlazol-2-yl) -benzamlde,
4-[(2-^oxy-eth^amino)-methyl]-N-(4-methD*y-7-inorpholin-4-yl-ben20thia2ol-2-yl)-
benzamide,
N-(4-methoKy*7-inorpho]in-4-yl-benzothiazoI-2-yl)-4-methylaminonicthyl-benzainide,
4-(2-dimethylainino-ethylsu]fanylrnethyI)-N"-(4-raethaKy-7-morpholin-4-yi-
benzotbia2ol-2-yI) -benzamide,
4-{[(2-ethoxy-ethi4)-ediyl-amino]-methyl}-N-(4-methoxy-7-morpholin-4-yI-
benzothiaZol-2-yl)-benzamide,
4^f[(2-«iox^-ethyl)-methyl-ainiijo]-meliiyl}-N-(4-methoxj"-7-morpho]in-4-y!-
benzothiazoI-2~yl) -benzamide,
4-(2-methoxy-d:hc)xymethyl)-N benzamide,
4-methoxymethyl-N-(4-metho3cy-7-morphoiin-4-yl-benzothia2ol-2-yl)-benzamide,
N-(4-merhoxy-7-thiomorpholin-4-yl-benzothiazoI-2-yl)-benzamideand
[4-(4-metho^-7-morpholin-4-y]-benzothia2oI-2-ylcarbanioyl)-benzyl]-meth^-catbamic
acid methyl aster.
6. The compounds of formula IA in accordance with claim 1, wherein R" is phenyl, substituted by a optionally substituted -(CR^Ja-five to seven membered aromatic or non aromatic heterocycle.
7. The compounds of formula IA in accordance with claim 6, which compounds are
44midazol-l-ylmetiyI-N-(4-methffKy-7-phenyl-beii20thiazol-2-y3)-benzarriide!
4-(4-HychQ^-pipexidin-l-ylmethyt)-N-(4-methoxy-7-phenyl-beriZothiazol-2-yl)-
benzamide,
4-[I4]dia2epan-l-y]methyl-N-(4-raethoxy-7-phenyl-ben2othiazol-2-yl!)-benzainicle,
4-(3(S)-dunirthylarmno-pyrroIidin-l-yImethyI)-N-(4-methoxy-7-pheny]-benzothiazol-2-
yl)-benzamide,
N-{4-methosy-7- f 2- (6-methyl-pyridin-3-yl)-thiai:ol-4->i] -benzothiazol~2 -yl} -4-
pyrrohdin-1 -yl-methyl-benzamide,
N-{4-methoxy-7-thiophen-2-yl-ber^oi^ia2nl-2-yl)-4-pyrrolidin-l-yl-methyI-beQzamide,
N-[4-metho^-7-(2-p>Tidin-2-yl-thia2«l-4-ylJ-benzothiazol-2-yl]-4-pyrrolidin-l-yl-

methyl -benzamide,
4-cWoro--N-(4-methoxy-7-morpholin-4--yl--bciizothiazol--2-)"l)-3-pyrroIidiii-l-yl-inethyl-
benzamide,
N - (4-methoxy-7-morphoHn^-yl-benzothiaZol-2-yI)-3-pyrrolidin-. 1 -yl-methyl-
benzamide,
N- C4-methoxy-7-morpholin-4-yl-benzQthiazol-2-yI )-4- (2-roethy!-iinidazol-1 -yi- methyl )-
benzamide and
N-(4-methoxy-7-morpholin-4-y]-benzothiazol-2-yI)-4"(4-methyl-piperazin-l-yI-
methyl)-ben2amide.
8. The compounds of formula IA in accordance with claim 1> wherein R* is an oprionaJly substituted five or six membered aromatic or non aromatic heterocycle.
9. The compounds of formula IA in accordance with claim 8, wherein the five or six
membered aromatic or non aromatic heterocycle is morpholine or piperazine.
10. A process for preparing a compound of formulas l-A as claimed in claims 1-9
which process comprises

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Patent Number

211734

Indian Patent Application Number

IN/PCT/2002/2070/CHE

PG Journal Number

52/2007

Publication Date

28-Dec-2007

Grant Date

09-Nov-2007

Date of Filing

12-Dec-2002

Name of Patentee

F. HOFFMANN-LA ROCHE AG

Applicant Address

124, Grenzacherstrasse, CH-4070 Basle,

Inventors:

#	Inventor's Name	Inventor's Address
1	ALANINE, Alexander	11a, rue de Bale, F-68440 Schlierbach,
2	FLOHR, Alexander	142 St. Galler-Ring, CH-4054 Basle,
3	MILLER, Aubry, Kern	72A Alvarado St, San Francisco, CA 94110,
4	NORCROSS, Roger, David	Alte Saline 20, CH-4310 Rheinfelden,
5	RIEMER, Claus	Optizstrasse 5, 79110 Freiburg,

PCT International Classification Number

A61K 31/427

PCT International Application Number

PCT/EP2001/006506

PCT International Filing date

2001-06-08

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	00113219.0	2000-06-21	EUROPEAN UNION