Title of Invention

NEW COMPOUNDS USEFUL FOR THE TREATMENT OF OBESITY, TYPE II DIABETES AND CNS DISORDERS

Abstract

ASBSTRACT 3052/CHENP/2004 The present invention relates to compounds of the general formula (I), wherein P is sulfonamide; and A, B, W, X, Y and R3 are as defined in the description; to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the prophylaxis and treatment of medical conditions relating to obesity, type If diabetes, and/or CNS disorders, to achieve reduction of body weight and of body weight gain.

Full Text

RELATED APPLICATIONS This applicadoQ claims priority to Swedish application number 0201925-5, filed on June 20,2002, Swedish plication number 0202908-0, filed on October 1,2002, Swedish pUcation number 0202181-4, filed on July 11, 2002, Swedish application number 0300357-1, filed on February 10,2003, U.S. provisional jplication 60/406,120, filed on August 26,2002, U.S. inrovisional apphcation 60/434,010, filed on December 17,2002, and U.S. provisional pHcation 60/464,701, filed on April 23,2003, the contents of which are incorporated herein by reference. TECHNICAL FIELD The present invention relates to substituted sulphone and sulphonamide compounds, to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the prophylaxis and treatmait of medical conditions relating to obesity, type 2 diabetes, and/or disorders of the csitral nervous systHn (CNS), to achieve reduction of body weight and of body weight gain, as well as for cosmetic use. BACKGROUND ART Obesity is a condition characterized by an increase in body fat content resulting in excess body weight above accepted norms. Obesity is the itiost important nutritional disorder in the western world and rqDreseots a major health problem in all industrialized countries. This disorder leads to increased mortality due to increased incidences of diseases such as cardiovascular disease, digestive disease, respiratory disease, cancer and type 2 diabetes. Searching for compounds, which reduce body weight has been going on for many decades. One line of research has been activation of serotoninergic systeoK, either by direct activation of serotonin receptor subtypes or by inhibiting serotonin reuptake. The exact receptor subtype profile required is however not known. Serotonin (5-hydroxytryptaaiine or 5-HT), a key transmitter of the periptoal and central nervous sjtem, modulates a wide range of physio local and pathologica] functions, including anxiety, sle legilation, aggression, feeding and depression. Multiple serotonin receptor subtypes have h&ea identified and cloned. One of these, the S-HTg receptor, was cloned by several groups in 1993 CRuat, M. et al. (1993) Biochran. Biophys. Res. Commun.193:268-276; Sebbea,M. et aL (1994) NeuroRort 5:2553-2557). This receptor is positively coi>led to adenyljd cyclase and displays affinity for antidepressante such as clozapine. Recently, the effect of 5-HT6 antagonist and S-HTg antisense oligonucleotides to reduce food intake in rats has been reported (Bentley, J.C. et al. (1999) Br J Pharmac. Siqjpl. 126, P66; Bentley, J.C. et al. (1997) J. Psychophaimacoi. Suppl. A64,255; WoolleyM.L. et al (2001)Neurophaimacology). Compounds with enhanced affinity and selectivity tor the 5-HTg receptor have been idenfiSed, e.g. in WO 00/34242 and by Isaac, M. et al. (2000) 6-Bicyclopiperazinyl-l-arylsulfonylindoles and 6-Bicyclopipendinyl-I-arylsulfonylindoles derivatives as novel, potent and selective 5-HTs receptor antagonists. Bioorganic & Medicinal Chemistry Letters 10: 1719-1721 (2000). INFORMATION DISCLOSURE J. Med. Chem. 1970,13(4), 592-598 describesN-(4-{[2-(diefliyIanmio)ei3iyI]amino}-l- nhthyl)amideB;N-(5,6,7,8-Tetrahydro-4-[(3-piperidiiiopropyl)amino]-l- nhthyl}amides and related amides and urea derivatives as schistosomicides, WO 99/42465 discloses sulphonamides derivatives that bind to the S-HTg receptor and that can be used for fbe treatment of CNS disorders such as anxiety, depression, epilepsy, obsessive compulsive disorders, cognitive disorders, ADHD, anorexia and bulimia schizophrenia, drug abuse. WO 01/32646 Al discloses compounds that bind to the S-HTg receptor and liiat are used for the treatment of CNS disorders and which inter alia may be used for the treatment of eatkig disorders. wo 99/37623 A2 Sscloses compounds that bind to Uie 5-RTQ receptor and fcat are used for the treatment of CNS disorders and which inter alia may be used for flie treatment of eating sordsrs. WO 99/42465 A3 discloses compounds that bind to the S-HTg receptor and that are used for liie teeatmer: of CNS disorders and which inter alia may be used for the treatment of eating disorders. EPO 815 861 Al discloses compounds Ihat bind to te5-HTgrecqjtor and that are used for the trsatment of CNS disorders. WO /02502 A2 discloses compounds that bind to the 5-HTg receptor and that are used for the treatmrait of CNS disorders and which inter aha may be used for e treatment of eating disorders. WO 98/27081 Al discloses coiipDunds that bind to &e S-HTg receptor and &at are used for flie treatment of CNS disorders and which inter alia may be used for the treatment of eating disorders. EP 0701819 discloses compounds that bind to the 5-HTjj) receptor and that are used for the treatment of CNS disorders and obesity, US 6,191,141 and WO 01/12629 disclose compounds that bind to the S-HTg recqntor and fliat are used for the treatment of CNS disorders. DISCLOSURE OF THE INVENTION It has suiprisingly been found Qiat the compounds of fomiula (I) show afSnity for the 5~ HTg receptor as antagonists at low nanomolar range. Compounds according to the invention and their pharmaceirtically acceptable salts have S-HTg receptor antagonist, agonist aad partial agonist activity and are believed to he of potential use in the treatment or prophylaxis of obesity and type 2 diabetes, to achieve reduction of body weight and of body weight gain, as well as in the treatment or prophylaxis of disorders of the central nervous system such as anxiety, depression, panic attacks, memory disorders, cognitive disorders, sleep disotd, migraine, anorexia, bulimia, binge disorders, obsessive compulsive disorders, psychoses, Alzheuner's disease, Parkinson's disease, Huntington's chorea and/or schizophrmia, Attention Deficit Hyperactive Disorders (ADHD), drug abuse. The reduction of body weight and of body weight gain (e.g. treating body-weight disorders) is achieved inter alia by reduction of food intake. As used herein, the term "body weight disorders" refeis to the disorders caused by an imbalance between, energy intake and mergy expenditure, resulting in abnormal body (e.g., excessive) weight. Such body weight disorders include obesity. Definitions Unless otiiesTOse stated or indicated, the term "C1 alkyl" (or "C2-6 alkenyl") denotes a straight or branched hydrocarbon chain group having fiom 1 to 6 carbon atoms (or 2 to 6 caibon atoms). Exanqiles of said lower alkyl include methyl, ethyi, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, t-butj4 and straight- and branched-chain pentyl and hexyl. Alkenyl groups have one or more double caibon-carbon bonds in tbe chain. Unless o-therwise stated or indicated, the term "C1-g alkoxy" denotes a straight or branched alkoxy group having fiom 1 to 6 carbon atoms. Examples of said lower alkoxy include meftioxy, elboxy, n-propoxy, iso-propoxy, n-bntoxy, iso-butoxy, sec-butoxy, t-butoxy and straight- and braached-chain pentoxy and hexoxy. Unless otherwise stated or indicated, the term "C1-g alkoxyalkyl" denotes a straight or branched alkoxyalkyl groiq) having from 1 to 6 carbon atoms. Examples of said lower alkoxyalkyl include methoxymethyl, ethoxymefliyl, iso-propoxymethyl, n-butoxymethyl, t-butoxyethyl and straight- and branched-chain pentoxymethyl. The expression "C2-6 aJkenyl" as used herein refers to straight-chained and branched alkenyl groups containing from 2 to 6 carbon atoms. Typical examples include vinyl, allyl, 2,3-dimaiiylallyl, 1-butenyl groups, 1-pentenyl, and 1-hexenyl groups. The expression "C2.5 allcynyl" as used herein rsf&3 to s&aigbt-chained and branched dkynyl groups containing from 2 to 6 caibou atoms. Typical exanles include etiiynyl, 1-propynyl, l-butynyL, 1-pentynyl, and 1-hexynyl groups. Unless othMwise stated or indicated, the term "halogen" shall mean fluorine, chlorine, bromine or iodine. The term "alkylhalide" refers to sa alkyJ groap substituted with one or more halogen groups (e.g., F, CI, Br, I). The temi "C3.7 cycloalkyl" denotes a cycUc alky! group having a ring size from C3 to Cy, which can be saturated or partially unsaturated. Examples of said cycloalkyl include cyclopropyl, cyclofautyl, cyclopaityl, cyclopeitenyl, cyclopenladienyl, cyciohexyl, methylcyclohexyl, cyclohexenyl, cyclohexadienyl, and cycloheptyl The term "€5,20 cycloalkenyl" denotes a cyclic alkenyl group having a ring size from C5 to C1o-Examples of said cycloalkenyl include 1-cyclopentyl, 2-cyclopentenyl, 1- cyclohexeayL, 1-cycIohepenl, 1-cycIooctenyl, 1-cyclononenyl, and 1-cycIodecenyI groups. The temi "heterocyclic" refers to a hydrocaibon ring system containing 4 to 8 ring members that have at least one heteroatom (e.g., S, N, or 0) as part of the ring. It includes saturated, unsattirated, aromatic, and nonaromatic heterocycles. Suitable heterocyclic groups include thienyl, furyl, pyridyl, pyrrolidinyi, imidazolyl, pyrazolyl, piperidyl, azepinyl, morpholinyl, pyranyl, dioxanyl, pyridazin>1, pyrimidinyl, and piperazinyl groups Unless otherwise stated or indicated, the term "ary!" refers to a hydrocarbon ring system having at least one aromatic ring. Examples of aryl groups include phenyl, cinnamyl, pentaleny], indenyl, I-naphfliyl, 2-naphthyl, anthryl and phenanthryl. Tlie tenn "heteroaryl" refes to a hydrocarboc ring system having at hast erne aromatic ring which confcms at least one hetoatom such as 0, N, or S, Examples of heteroaryi groups include fiiryl, pyiiolyl, thienyl, oxazol) imidazolyl, tiiiazolyl, pyridinyl, pyrimidinyl, quinazolinyl, and iodolyl groiqis. Compounds of Formula 0 heteroaiy! ring, said heteroaryi ring comprising one or two atoms selected from the group consisting of niirograi, sul&r and oxygen, prilh the proviso that when D contains an oxygen atom, D is heteroaryi; each W is indqjendently -N-, -(CH)-, or -C- provided that not more than three groups W I are -N- in both rings A and B together; P is any one of foimnla (a), (b) or (c) and P ar«J R can be attached to any caibon atom that allows the substitution in one of eifeea" ibe A- or B-ring, or when ring A contains at least one nitrogm atom and P is (c), -. iheai P can also be attached to any nitrogen in ring B that allows the substitution; the dashed bonds denote that P and R, respectively, may be attached to either fee A or B ring; but each P or R may not be simuitaneousiy bound to both rings A and B; RMS (a)Cj.6aikyl, (b) C1,a alboxyalkyl, (c) strait-chained or branched C1. hydroxyalkyl, (d) straight-chained or branched C. alkylhalides, (e) aryl carbonylmeliiji, (f) C3-7 cycloalkyl, which is optionallypartially unsaturated, (g) C3.7 cycioalkyl-C1-s alkyl, wherein the cyclic ring is optionally partially imsatuiated, or (h) a group Ar, wherein AT is (a) phenyl, (b) l-nhttiyl, (c) 2-naphthyl, (d) aryI-C1.6 alkyl, (e) chmamyi. (f) a 5 to 7-aiembered, optionally aromatic, partiaUy saturatBd or completely saciirated, mono- or bi-cyciic heterocyclic ring, each containing 1 to 4 heteroaioms, selected S:om oxygen, sulfur, and nitrogen, (g) a bicyclic ring system comprising at least one heterocyclic ring according to (if) and a wherein the group Ar is substifuted in one or more positions with (a)H,XorY,or (b) a 5 to 7-mem1>ered, optionally aromatic, partially saturated or completely saturated, heterocyclic ring each containii 1 to 4 heteroatoms selected from oxygMi, nitrogao or sulfur; Ris (a)H, (b)C1allcyl, (c) C2.6 alkoxyaHcyl, (d) strmgjit or branched C1-6 hydroxyalkyl, or (e) straight or branched C1- alkylhaUdes; (f) a group Ar, wherein v is 0-2, X and Y are indjendeatly (a}H, (b) ha!og«i, (c)CwaJkyl, (d)CF3. (e) hydroxy, (f) C1.6 alkosy. (g) C2.6 alkenyl, Ol) phenyl, (i) phenoxy, 0) benzyloxy, (k) benzoyl, (l)-0CF3, (m) -CN, (n) strght or branched Cu hydroxyalkyl, (o) straight or branched C1-6 aikylhalides, (p) -NH2, (q)-NHR*, (r)-NR*R (s) -NO2, (t)-CONR' (u) -NHS02R(v)-NR'C0R (x) -SO2NRV, (z)-C(=0)R (k) -C02R or (l) -S(0>,R', wherem n is 0,1,2 or 3, (ac)-S-(C1)aIkyl,or (ad}-SCBf,aad R* and R are indepKideiitly (a)H, (b) Cu alkyl, (c) C3.7 cycloalkyl, or (d) AT, as defined above for R' ; altesmatively, R" and R are linked to form a poiq) -CH20C3I2-, -CH2CH20CH2CH2- or (CH2)3.s; wherein R is optionally substituted on each carbon atom that allows the substitution with Rq groups, wherein Rq is independently H, or (C1) alkyl, and wherein two Rq groups can be present on the same carbon atom simultaneously, wherein q=I,2,3,4,5or6, m = 1 or 2, and n = 0, lor2; R is independentiy (a)H,. (b) linear or branched CJ-A alkyl. (c) benzyl, (d) -CH2-CH2-OH, or (e) -CH2-CHi-0-C,-6 alkyl; can be attached to the same ring or to different rings of rings A and B; containing a N atom, the N atom in Ar cannot be attached to tlie S atom in P; with the proviso that: ■when rings A. and B aie both phaiyl, P is any one of formula (a) or (c) substituted is pDsition 7 on the nhthalene ring, then R' is not substituted in position 1 on the naphflialene ring; and with the proviso that: whai ring D is a pyrrole ring, P is of the formula (c), thrai R is not of the fbrmnla wherein Pi-Pg denote the position on the naphflialene ring. A pyrrole ring, as connected to an A ring, has the following position mmibers: I wherein P1-P3 denote the position on the pyrrofe ring. It is preferred that: R'is (a) C1.6 alkyl, or (e) a group Ar; 0 Aiis (a) phCTiyl. (b) 1-naphthyl, (c) 2-naphthyi, or (i) a 5 to 7-meiDbered, optionally aromatic, partially saturated CM: conqiletely saturated, heterocycJic ring containing 1 to 4 heteroatoms, selected from oxygen, nitrogen and sulfiar, wherein the group Ar is substituted in one or more positions with Ca)H, (b) halogen, (c) C1.6 alky], Cd)-CF3, (f) CM aUcoxy, (g) C2.6 alkenyl (preferably C2-4 alkenyl), a)-OCFj, (m) straight or branched C1.6 hydroxyalkyi, (n)phenylloxy, (o) benzyloxy, Cv)-NR'COR (x)-S02IRR Z)-C(=0)Rah) -S(0XR\ wherdn n is 0,1,2 ot 3; ac) -S-(C1) alkyl, or ;ad)-SCF3; [a) H, or (b)C1.6 alkyl; or R' and S? are linked to fonn a group -CHjCHzOCHzCHi-; XandYareH; R and R are each indmdently H or C1.3 alkyl; and R is indepaidenlly (a)H, (b) C1-6 alkyl (preferably C1.3 alkyl), in particular methyl, (d)-CH2-CH2-OH,or {e)-CH2-CH3-OCH3. R. is indepeoiiently (a)H, (b) C1.3 alkyl, (d) -CHj-C3l2-OH, or (e)-CH2-CH2-OCH3. It is preferred that R is H or methyl. It is also preferred that R. is piperazine; homopiperazine; 2,6-diroethylpiperazine; 3,5-dimethylpiperazine; 2,5-dimefliylpiperazine; 2-methylpiperaziiie; S-methylpipeyazine; 2,2-dimethylpiperaziiie; 3,3-dimethylpiperazine;piperidine; 1,2,3,6-tetrahydro-pyrazine; or 4-pyrrolidin-3-yloxy. It is preferred that flie groups Y and X are attached to any unsubstituted carbon atom. It is prefeired tiiat D is pyrrolyl, thienyl or furanyl. It is preferred that y = 0 and x = 2. Another object of the present invaitbn k a compound of the general formula (HT) wherein R', x,y,X, and Y are as defined in claim 1, and R is as defined in claim 2. It is prefeited that y = 0 and x = 2 wherein Pis of the formula (C),R',X, yjX, and Y are as defined in claim 1, and R. is as defined in claim 2, and wherein D is a five-membered heta-oaryl ring, said ring comprising one or two atoms selected firom the group consistii of nitrogen, sulfur and oxygen; and when the heteroaryl ring comprises one or two nitrogen atoms, a group R is attached at any nitrogen atom which allows the substitution. It is also preferred that D is fiuran and P is attached to the D ring, giving a skeleton as any of the following: Another object of the present invention is a compound of the geaieral fonnula (V) wherein P is of the formuia (c) as defined in claim 1, R', X, y, X, Y, and R are as defined in claim 1, and wherein D is a five-memba heteroaryl ring, said heteroaryl ring comprising one or two atoms selected Sxim flie grovip consisting of nitrogen, sulfur and oxygen; and whai flie heteroaryl ring conrises one or two nitrogen atoms, a group R* is attached at any nitrogen atom which allows the substitution. wherein P is of the formula (a) or (b) as defined in claim 1, preferably wherein R. is H, X, Y, and R"* are as defined m claim 1, and wha-ein D is a five-merabaed heteroaryl ring, said heteroaryl ring comprising one or two atoms selected fi'om the group consisting of nitrograi, sulfur and oxygen; and when the heteroaryl ring cotcrises one or two nitrogen atoms, a groiq) R is attaclied at any nitrogen atom which allows &e substitutioa (c) benzyl, (d) -CH2-CH2-OH, or (e> CH2-CH2-O-CH3, and wherein P is of the formula (a) or (b) as defined in claim 1, prefsiably wherein R is H, X, Y,andR' are as defined in claim 1. Anoflier otaj ect of ibs present invention is a compound of Qie general fonniiia pQ wbarein P is of the formiila (a) or (b) as defined in claim 1, preferably wherein R is H, X, Y, and R' are as defined in claim 1. or a pharmaceutically acceptable salt thra-eof wherein P and R are attached to the same ring or to different rings of rings A and B, wherein A, B, Y, P, and Rj are as defined m claim I. Preferred compounds of the formula (IT) are 6-Benzenesiilfonyl-4-piperazin-l-yl-qiiinoiine hydrochloride; 6-[(2-Fluorophenyl)sulfbnyl]-4-pipa-a2in-l-ylquinoline hydrochloride; 6-(l-NhthylsulfonyI)-4-pipera2in-l-yIqiiinoline hydrochloride; 6-[(3,4-Dicblorophaiyl)sulfony!]-4-piperazm-l-ylqiiinohne hydrochloride; 6-[(3,5-Diiiiethylphenjd)sulfonyl]-4--piperazin-l-ylquinoIine hydrochloride; 6-[(2-ChIoto-6-methylphBny!)siitfonyl]-4-piperazin-l-ylquinoiine hydrochloride; 6-[(4-C!itofopheny])sulfonyI]-4-pipan-l-ylquinoline hydrochloride; 6-[(2-Metbyl,4-tert-butyl-phen5l)si]lfony!]-4-pipera2in-l-ylquinoline hydrochloride; 6-[(3,4-Dimethsdphen;d)sulfonyl]-4-piperazin-l-ylquJnoIine hydrochloride; 6-[(2-DichlorophaiyI)sulfon;d]-4-piperazm-l-ylquinoline hydrochloride; 6-[(4-tert-Biityhenyl)stilfbnylJ-4-piperaz!n-l-ylqiiinoIine hydrochloride; 6-[(4-Isopropylphenyi)sulfonyl]-4-pipera2itt-l-ylquinoline hydrochloride; (4-Piperazin-l-yl-6-{[4- Preferred compounds of the formula (HI) are 7-(2-ChIoro-6-methyI-benzraiesulfonyI)-l-piperazin-l-yl-isoquinoline hydrochloride; 7-(2-r-Butyl-benzenesuIfonyI)-l-piperazin-l-yl-isoquinoline hydrochloride; 7-(3,4-Dichloro-benzKiesu!fonyl)-l-piperazm-l-yl-isoquinoline hydrochloride; 7-(2,4-DimethyI-ben2enesiilfonyI)-l-piperazin-l-yl-isoquinoline hydrochloride; 7-(2,5-Dimethyl-ben26nesulfonyl)-l-pipera2ia-l-yl-isoquinoline hydrochloride; 7-(p-Chloro-benzenesulfonyl)-l-piperazin'l-yI-isoquinoline hydrochloride; 7-Benzenesulfonyl-l-[l ,4]diazepan-l -yl-isoqumolineydrochloride; 7-(4-tert-Butyl-benzenesulfonyl)-I-[l,4Jdiazepan-I-yI]-isoquinoline, hydrochloride; 7-(2-ChIoro-6-me&yl-benzKiesulfDnyl)-l-[l,4]diazepan-l~yl]-isoquinoline hydrochloride; 7-(3,5-DimethyI-ben2enesulfonyl)-l-[],4]diazepan-l-yI]-isoquinoline hydrochloride; 7-(3,4-DicMoro-benzeiiesu!ibnyl)-l-[l,4]diazepan-l-yl]-isoquiiioIine hydrochloride; 7H;4-Chloro-beazeoesulfocyl)-l-[l,4]diazepaQ-l-yI]-isoquinoline hydrochloride; 7-(3,4-Dkaefcyl-bai2eQesulfonyl)-l-[i,4]diazepan-l-yl]-isoqtimohne hydrochloride; 7-(2-tat-EutyI-bra2enKiulfoiiyl)-1 -[1,4]diazepan- l-yl]-iBoqviiaoime hydrocUoride; 7-Baizeiiesulfony3-l-piperazin-yl-isoquinoIuie hydrochloride; and 7-(4-tot-Butyl-benzenesulfonyl-l-piperazin-yl-isoqiiijioiine hydrochloride Preferred compouods of the fonnula (IV) are 4-(l,4-Diazan-l-yl)-2-(phen>1sii!fonyI)lhiaio[3-c]pyridine hydrochloride; 4-(l ,4-Dia2epan- l-yl)-2-[(3,4-dichlorophenyl)siiIfonyl]thieQo[3,2-c]pyridine hydrocKloride; 4-(l,4-Diazepan-l-yl)-2-[4-tert-butylphenylsulfonyI)thieno[3,2-c]pyridine hydrochloride; 4-(l,4-Diazepan-l-y])-2-[4-tKt-butylpheaylsuIfonyl)thieno[3,2-c]pyridine hydrochloride; 4-(U4-Diazepan-l-yl>2-[3,4H3imethylphenylsTjlfonyl)thieiio[3,2-c]pyridine hydrochloride; 2-[(4-BroinophenyI)sulfi)nyl3-4-(I,4-diazepan-l-yI)fhieiio[3-c]pyridine hydrochloride; 2-5'henylsulfonyl)-4-piperazm-l-ylthieQo[3,2-c]pyridme hydrochloride; 2-3-Methoxy-benzenesiilfonyI)-4-piperazm-l-yl--thieQo[3,2-c]pyridme hydrochloride; 2H;4~Metboxy-benzeHesulfenyi)-4-pipCTa2in-l-yl-thieiio[3,2-c]pyridine hydrochloride; 4-Piperazm-l-yl-2-{[4-trifluoroineQiyl)phenyl]sulfonyl}thieno[3-c]pyridine hydrochloride; 2-[[2-tert-ButyIpheny!)siitfonyl]-4-piperazm-l-ylthieiio[3-c]pyridme hydrochloride; 2-[(3,4-DicUoropheny!)suIfonyl]-4-piperazm-l-ylthie!io[3,2-c]pyridine-2-EiiIfona]md6 hydrochloride; 2-[{4~tert-Buty[pheayl)sulfonyl]-4-piperaziD-l-yIthiaio[3-c]pyriditie hydrochloride; 2-(l-Nhthyl suifonyl)-4-piperazi]i-l-ylthieno[3-c]pyridioe hydrochloride; 2-[C3-FluorophenyI)siilfonyl]-4-piperazm-Uylfliieno[3,2-c]pyridiBe-2-sulfonamide hydrochloride; 2-OVIesitylsu!fonyl)-4-piperazm.-l-ylthieao[3,2-c]pyridinc hydrochloride; 2-[(2-Metlioxypheiiyi)Bulfonyl]-4-piperazin-l-ylthieno[3,2-c]pyridme hydrochloride; 2-[(2,4-Dimefhoxyphen.yi)sulfon.yl]-4-p)eraziri-l-ylthseno[3,2-c]pyridirie hydrochloride; 2-K2,4-DjrnetbylpheiiyI)sulfbQyi]-4-pipera2m.-I-y]thieiio[3,2-c]pyridine hydrochloride; 2-K2,5-DimethyIpheiiyl)sulfonyl]-4-piparazin-l-yltbieno[3,2-c]pyridine hydrochloride; 2-[(2-Eay]phenyl)su]foaj]-4-pipeiazin-l-y]aiirao[3,2-c]pyridme hydrochloride; 4-(Piperazmyl)-2-(3-methoxybeiizyl-sulfonjd)-thiaiopyridine hydrochloride; 2HBeiizylsulfony!)-4-piperaziii-l-ylthieiio[3-c]pyridiiie hydrochloride; 4-Piperazin- I-yl-2- {[4-CtiMuoromethyI)benzyI]suIfbnyI}thieno[3,2-c]pyridine hydrochloride; 2-j;{3-Bromobeaizyl)sulfonyl]-4-piperazin-l-ylthieno[3,2-c]pyridme hydrochloride; 2-[{2,3-Difluon)baizyl)sulfonyl]-4-piperm-l-ylthieiio[3,2-c]pyridine hydrochloride; 2-[(4-Bromob6n2yI)sulfony2]-4-pipa'azm-l-ylthieno[3,2-c]pyridine hydrochloride; 2- {[2,5-bis(TrifliioromefliyI)beazyl]sulfonyl}-4-piperaziii-l -ylthienQ[3,2-c]pyridine hydrochloride; 2-[(4-MethyIbenzyI)siiIfonyi]-4-piperazin-I-y!thieno[3,2-c]pyridine hydrochloride; 2- {[5-Chloro-2-(triflaorom6fliyl)beii2yl]siilfonyl} -4-pipM-azin-l-ylthienD[3-c]pyridirLe hydrochloride; 2-[(3,S-DimethoxybenzyI)sulfonyl]-4-piperazm-l-ylthieno[3,2-c]pyridine hydrochloride; 2-[(2-Naph&ylme£fiyI)sij]fony]]-4iperaziii-]-yllhieno[3,2-£]pyridinehydrodiloride; 4-Piperazin'I-yl-2-{[4-(l,2,3-thiadiazol-4-yl)benzyl]sulfonyl}thieBo[3,2-c]pyridine hydrochloride; I-(4-PyrroIidm-I-yIpheiiy])-2-[(4-piperazine-I-yithieno[3;!-c]pyridm-2-yl)siiIfony]] eflianone hydrochloride; and l-[4-(pje1liylainuio)phenyl]-2-[(4-piperazine-l->lthieEo[3,2-c]pyridm-2-yl)siilfonyl] ethaaone hydrochloride, Also preferred compounds of Hie formula {IV) are l-(4-MethylphenylsulplionyI)-4-piperaziii-l-yl-lH-pyrrolo[3,2-c]pyridine hydrochloride; I-(3-Chloro-2-methyIphenyIsuipfaotiyi)-4-piperazin- 1-yi- Iff-pyrrolo [3,2-c]pyridine hydrochloride; l-(3,4-DirnethoxypheiiylsiilphoriyI)-4-piperazin-l-yl-li?--pyrrolQ[3,2-c]pyridme hydrochloride; 4-(4-Kperazin-I-y]yrro]o[3-c}pyridine-l-sul&2iyl}-beazonJtiileh}ochloride; 1 -(4,5-Dichloro-thiophene-2-sulfonyl)-4-piperazm-l -yl-lH-pynoio[3,2-c]pyridine hydrochloride; 4-(4-Methylpiperazm-l-yI)-A'- (2-tMen-2-yIetIiyI) thieno [3,2-c] pyridine-2-sulfonaniide hydrochloride; 4-(4-Methylpipa:azin-l-yl)-A'- [I-Cl-naphthyl) ethyl] thieno [3-c] pyridine-2-su!fonamide hydrochloride; 4-(4-Methyiperazin-l-yl)-7V- C4-he3£ylpheiiyi) thieno [3,2-c] pyridme-2-sulfonamide hydrochloride; N- (3-Chlorobeii2yI)-4-(4-methylpipera2iii-l-yI) Ihieno [3,2-c] pyiidine-2-suifonainide; 4-(4-Me&ylpiperazin-I-yl)-JV- [I-(4-iluonjpheiiyl) ethyl] ihieno [3-c] pyridine-2- sulfonamide hydrochloride; N- (2,3-Difluaroben2yl)-4-(4-ineQiylpiperaziD-l-yi) thieno 3,2-c] pyridine-Z-sulfoimnide hydrochloride; 4-(4-Metiiylpiperazin-l-yl>-JV- (4-chloTO-2,5-diniettioxyph.eoyl)thie3Mi [3-c]pyridine-2- sulfonamide hydrochloride; 2-Bromo-4- (4-meth3pipera!aii-l-ji)-W- (2-cycloh6x-l-en-l-ylethyl) fcieno [3-c] pyridine-3-sulfoiiamide hydrochloride; 2-Bromo-4- (4-meQiylpiperazin-l-yl>-A'- [(15)-]-(2-nhQiyl) ethyl] Meno [3-c] pyridine-3-sulfoEainide hydrochloride; 2-Bromo-4- (4-methyipip:azm-l-yi)-N- [l-(4-fluorophenyl) ethyl] thieno [3,2-c] pyridine- 3-sulfonamide hydrochloride; 2-BromO'4- (4-m6thylpiperazin-I-yl)-A'- (2,4,5-triinethoxypheQyI) thieno [3,2-c] pyridioe- 3-sulfonanude; N-(3,4-DichIoxoplienyl)-4-piperazin-l-y]thieno[3,2-c]pyridine-2-suIfonamid6 hydrochloride; N-(2,4-DifluorophenyI)-4-piperaziii-l-ylthieno[3,2-c]pyridiQe-2-sulfbiiaraid6 hydrochloride; 4-Piperaztn-l-yl-N-[-3-(trifluorome&y])phenyl}thieoo[3,2-c]pyridme-2-siilfonarDide hydrochloride; N-(3-Ethylphenyl)-4-piperazin-l-ylthieno[3,2-c]pyridine-2-sulfonaniide hydrochloride; N-(3,4-Dime&ox.yphsiiyl)-4-piper32iitI-ylthieno[3-c]pyridine-2-sulfonarmde hydrochloride; K-(4-BTomo-2-niethyliwiyiy4-pipsraziQ-t-ylthien3[3,2-c3pyridine-2-su!fonamide hydrochloride; (4-PiperaziD-l-yl-thiea20[3 /drochloiide; ■PipsTizin-l-yl-thieno[3,2-c]pyridine-2-svilfomc acid (2-thiophen-2-yl-ethyl>amide /drochloride; -Pipenizin-l-yl-thieno[3,2-c]pyridine-2-sul£bmc acid (4-chloro-2,5-dimethoxy-phaayI)- tnide hydrochloride; -Piperazin-l-yl-thieno[3-c]pyridiue-2-salfemc acidphemethyl-amide hydrochloride; -Piperazin-l-yMliieno[3,2-c]pyridine-2-sulfonic acid (2,6-diethyl-pheiiyl)-aimde lydrochloride; t-PiperaziQ-l-yl-thien.o[3,2-c]pyridiBe-2-sulfonic acid (3-phenyl-propyl)-aniide lydrochloride; J-Piperazin-I-yi-thieno[3-c]pyridme-2-sulfonic acid (3,3- aydrochloride; i-Pjperazin-l-y]-lhieno[3,2-c]pyridiDe-2-sulfonic acid [2-(5-rDethoxy-lH-!Jido]-3-y])- ethyU-amide hydrochloride; 4-Piperazin-l-yl-tiueno[3,2-c]pyridine-2-sulFonic acid 4-tTifiuoromethyl-benzylamide hydrochloride; 4-Pipa3ziij-l-yl-thieno[3,2-c]pyridine-2-sulfonic acid benzyl-ethyl-amide hydrochloride; N-(3-Ethylphsnyl)-4-pipera2iii-i-ylthien.o[3,2-c]pyridiDe-3-sulfonainide hydrochloride; N-(4-Isopropylphenyl)-4-piperazin-l-ylthien.o[3,2-c]pyridiQe-3-siilfonaniide hydrochloride; NK4-Methylphenyl)-4-Cpyrrolidm-3-yIoxy)thieno[3,2-c]pyridine-2-siil&naimde hydrochloride; N-(4-MettiylphenyI)-4-(piperidin-4-yIoxy)thieno[3,2-c]pyridine-2-suIfon.aiiude hydrochioride; N-(2,3-DiatiorobenzyI)-4-piperaziQ-l-yltbieno[3,2-c]pyridine-2-suJfo2amide hydrochloride; N-(3-Ch]orobenzyI)-4-piperazm-l-yIlhieno[3,2-c]pyridine-2-su]fonamide hydrochloride; 4-Piperazin.-l-yl-thieQo[3,2-c]pyridine-2-sulfonic acid phenylamifte hydrochloride; 4-Piperazin-l-yl-thieno[3,2-c]pyridine-2-siilfoiiic acid (4-tert-hutyl-phenyl)-amide hydrochloride; 5-CMoro-N-[4-(piperidm-4-yIoxy)-l-nh1iiyI]a]iophene-2-siilfonamide hydrochloride; 4-CMoro-N-{4-[(3S)-pyriohdi]>3-yloxy]-I-nhthyl}beiizenesuifonaimde hydrochloride; and 4-CMoro-N-{4-[(3R)-pyriolidiii-3-yIoxy]-l-naphthyl}beiiizemesulfonaimde hydrochloride. Another object of flie present invaition is a process for the praration of a compound above, said method comprising the steps of: (a) Mitsonobu reaction of 4-nitro-l-iihthol with boc-protected 3-hydroxypyrrolidine or 4-hydroxypiperidine; . (b) reduction of the nitro group in the nitroojjhthalene obtained in step (a) to form an aminonaphfiialene derivative; and (c) synthesis of a sulfonamide by reacting the aminonaphthalene obtained in step (b) with a suitable sulfonyl chloride. carboxylic moiety to amine by Curtius rearrangeffient; reaction of the amine group with a sulpttonyichloride. member ring fused pyridine; introdnctloB of sulfonylchloride moiety by nucleophilic addition; reaction of sulphonylchloride moiety with an aniline to obtained a sulfonamide; aromatic nucleopMIic substitution of the chloro with a diamine. All diastereomeric forms possible (pure enantiomers, tautomers, racemic mixtures and unequal mixtures of two enantiomers) are within the scope of the invention. Such cofflpounds can also occur as cis- or trans-, £- or 2- double bond isomer forms. All isomeric forms are contemplated. The compoimis of the formulae (I) to (XJI) may be used as such cyr, where appropriate, as pharmacologically acceptable salts (acid or base addition salts) thereof The pharmacologically accqiteble addition salts as mentioned above are meant to comprise the thereutically active non-toxic acid and base addition salt forms tiiat ttie compounds are able to form. Compounds that have basic properties can be converted to Ihejr phamiaceutically acceptable acid addition salts by treating the base form with an appropriate acid. Exemplary acids include inorganic acids, such as hydrogen chloride, hydrogen bromide, hydrogen iodide, sulphuric acid, phosphoric acid; and organic acids sucli as acetic acid, propanoic acid, hydroxyacetic acid, lactic acid, pymvic acid, glycolic acid, maleio acid, malonic id, oxalic acid, benzenesuhonic acid, toluenesulphonic acid, methanesulphonic acid, trifluoroacetic acid, fumaric acid, succinic acid, malic acid, tartaric acid, citric acid, salicylic acid, p-aminosalicylic acid, pamoic acid, benzoic acid, ascorbic acid and the like. Exenq)lary base aldirion salt forms are the sodium, potassium, calcium salts, and salts with phannaceuticaliy acceptable amines such as, for example, ammonia. alkylamines, benzathine, and amino acids, such as, e.g. arginine and lysine. The term addition salt as used hein also conqirises solves which the compounds and sails thereof are able to form, such as, for example, hydrates, alcoholates and the like. For clinical use, die compounds of the invention are formulated into phannaceutical formulatioiis for oral, rectal, parenteral or other mode of aiministration. Pharmaceutical fcamoiatioiis are usually prepared by mixing the active substance, or a phannaceutically acceptable salt &ereot with convoitional pharmaceutical excipients. The formulatious can be flirther prepared by known methods such as granulation, compression, microraicapsulation, spray coati; etc. The formulations may be prared by conventional methods in the dosage form of tablets, csules, granules, powders, synqjs, suspaisions, suppositories or injections. Liquid formulations may be prepared by disolving or suspending the active substance in wato- or other soitable vehicles. Tablets and granules may be coated in a conventional manner. Another object of liie present invention is a compound above for use in thery. Anotlia- object of the present invention is a compound above, and for the case when rings A and B are both phenjd, P is any one of formula (a) or (c) substituted in position 7 on the naphthalene ring, and R' is substituted in position 1 on &e naphthaleae ling, for use in iiie treatmsit or prophylaxis of a 5-HTg receptor related disorder, such as obesity, type H diabetes, and/ca disotdas of the central najvovK system, to achieve reduction of body weight and of body weight gain. Another object of the present invention is a compound above for use in the treatment or prophylaxis of disorders of the central nervous system. Another obj ect of the present invention is a conqiound above, for the case when rings A and B are botti phenyl, P is any one of formula (a) or (c) substituted io -position 7 on the iiqihthalene ring, and R is substituted in position i on &e naphthalene ring, and for the case when ring D is a pyrrole ring, P is of tiie fonnula (c) and R is of the formula substituted in position 3 on the pyrrole ring, for use in the treatment or propliylaxis of obesity, to achieve reduction of body weit aud of body weight gain. Another object of the present invention is a pharmaceutical foimulation comprising a compound above as an active ingredient, in combiaation with a phannaceutically acceptable diluent or carrier. Another object of the present invention is a pharmeutical fonnulation comprising a compound above, and for the case when rings A and B are both phenyl, P is any one of formula (a) ot (c) substitated in position 7 on the naphthalene ring, and R is substituted in position 1 on the naphthalene ring, as an active ingredient, for use in the treatment or prophylaxis of a S-HTg receptor related disorder, such as obesity, type II diabetes, and/or disorders of the central nervous system, to achieve reduction of body weight and of body weight gain. Another object of the present invention is a compound above as an active ingredient, for use in. the Ireatmait or prophylaxis of disorders of the central nervous system. Another object of the present invention is a pharmaceutical formulation conrisiog a compound above, for the case when rings A and E are both phenyl, P is any one of foimula (a) or (c) substituted in position 7 on the naphthiieiie ring, and R. substituted in position 1 on the nhflialene ring, and for the case whei ring D is a pyrrole ring, P is of the formula (c) and R is of flie formula substituted in position 3 on the pyrrole ring, as an active ingredient, for use in tiie treatment or prophylaxis of type U diabetes. Another object of the present invention is a pharmaceutical formulation comprising a compound above, and for the case when ring D is a pyrrole ring, P is of the formula (c) and R is of the formula substituted in position 3 on the pyrrole ring, as an active ingredient, for use in liie treatment or prophylaxis of obesity, to achieve reduction of body weit and of body weit gain. Another object of the present invention is a method for the treatment or prophylaxis of a 5-HTg receptor related disorder, such aa obesity, type II diabetes, and/or disorders of the central nervous system, to achieve reduction of body wei and of body weight gain, which comprises administering to a subject (e.g., a mammal, a human, a horse, a dog, or a cat) in need of such treatment an effective amount of one or more compounds of any of flie formulae described abov (heir salt fonns or compositions ftiat include the compounds or their salt forms, and for the case when rings A and B are both phenyl, P is any one of formula (a) or (c) substituted in position 7 on the nhthalene ring, and R is substituted in position 1 on the nhthalene ring. Another ofaj ect of the present invention is a method for the treatment or prophylaxis of disorders of the central nervous system, which comprises administering to a subject in need of sud} treatment an effective amount of one or more compounds of any of the formulae described above, their salt forms or compositions ftiat include the compounds or tiieir salt forms. Another object of the present invention is a method for the treatment or prophylaxis of type H diabetes, which comprises administering to a subj ect in need of such treatment an effective amount of one or more compounds of any of the formulae described above, their salt forms or corf:5)OsiTions timt include &e compounds or their salt forms, for the ce when rings A and B are both phenyl, P is any one of formula (a) or (c) substituted in position 7 OR the naphflialene ring, and R is substituted in position I on the naphAalens ring, and for fee ce when ling D is apyrroleriag. Pis of the formula (c) andR is of the fonnula substi'ftited in position 3 on the pyrrole ring. Another obj ect of the present invention is a mefliod for flie treatment or prophylaxis of obesity, which comprises administering to a subject in need of such treatment an effective amound of one or more compounds of any of the formulae described above, their salt forms or corrqjositions that include ttie compounds or their salt forms, and for the case when ring D is a pyrrole ring, P is of the formula (c) and 'B? is of the fonnula substituted in position 3 on die pyrrole ring. Another object of flie present invention is a method for modulating S-HTg receptor activity, comprising administering to a subject in need thereof an effective amount of one or more compounds of any of the formulae described above, their salt forms or compositioiis that include the compounds or their salt forms. Another object of the presetit inventioa is the use of one or more conqrairnds of any of the fonnulae described above, their salt forms or corapositjoiis tiiat include the compounds or their salt forms, and for flie case when ring D is a pyrrole ring, P is of the fonnnla (c) and R is of Ihe formula substituted in position 3 on the pyrrole ring, for the manufacture of a medicament for use ii! Ihe treatment or prophylaxis of obesity, lo achieve reductictti of body weigfct and of body weight gain. The methods delineated herein can also include the step of identiiying that ftie subject is in need of treatmeait of obesity, type H diabetes, or disorders of the central nervous system, or in need of reducing body weight and of body weight gain. The invention further relates to cosmetic use of one or more compounds of any of tiie fonnulae described herein, for causing loss of weight, as well as cosmetic compositions Containing said compounds. StOl fiirther, the invention relates to a non-theremic metod for impriving ihs bodily appearance of a mamma], including a human, in which the method comprise orally administering to said mammal one or more compounds of any of the formulae described herein. "An effective amount" refers to an amount of a compound that confers a therapeutic effect on flie treated subject The fbEarapeutic effect may be objective (i.e,, measurable by some test or marker) or subjective (i.e., subject gives an indication of or feels an effect). For clinical use, the compounds of the invention are formulated into phaimaceutical formulations for oral, rectal, parenteral or othM mode of administration. Usually the amount of active compounds is between 0.1-95% by weight of the preparation, preferably between 0.2-20% by weit in preparations for parenteral use and preferably between 1 and 50% by wei in preparations for oral administratiorL The typical daily dose of the active substance varies wiftiin a wide range and will dend on various factors such as, for example, the individual requirement of each patient and the route of administration. Jn general, oral and parenteral dosages will be in the range of 5 to 1000 mg per day of active substance, preferably 50 to 150 mg per day. Processes for preparation In a furflier aspect the inveaition relates to methods of maldng compounds of any of the formulae herein comprising reacting any one or more of the compounds of the formulae delineated herein, includmg any processes delineated herem. The compounds of the fonnulae above maybe prepared by, or in analogy with, conventional methods, and especially according to or in analogy with the following methods. The chemicals used in the above-described synthetic route may include, for example, solvents, reagents, catalysts, protecting group and deprotecting group reagents. The mefliods described above may also additionally include stqis, either before or aiier the steps described specifically herein, to add or remove suitable protecting groups in order to ultimately allow synthesis of the compounds of any of the formulae described above, thehr salt forms, or comixtsitdons that include the compounds or their salt forms. Li addition, various synthetic steps may be performed in an alternate sequence or order to give the desired compounds. Synthetic chemistry transformations and protecting group methodologies (protection and deprotection) usefiil in synthesizing applicable compounds are known in the art and mclude, for example, those described in R. Larock, Comprehensive Organic Transformations, VCH Publishers (1989); T.W. Greene and P.G.M. Wuts, Protective Groups in Organic Synthesis, 2" Ed., John Wiley and Sons (1991); L. Fieser and M. Fieser, Fieser ondFieser's Reagents for Organic Synthesis, John Wiley and Sons (1994); and L. Paquette, ed., Encyclopedia of Reagents for Organic Synthesis, John Wiley and Sons (1995) and subsequent editions thereof. The specific examples beityw are to be coostroed as merely illustrative, and not limitative of ftte remainder of the disclosure in any way wliatsoever. Wittiout fiother elaboration, it is believed that one skilled in tiie art can, based on the descrq)tion herein, utilize fee present invraition to its iiillest extent, AH publicatioDS cited herein are hereby incorporated fay reference in their entirety. Methods 'H nuclear maetic resonance (NMR) and 'C NMR were recorded on a Bruker Advance DPX 400 spectrometer at 400.1 and 100.6 MHz, respectively. All spectra were recorded using residual solvent or tetramettiylsilane (IMS) as internal standard. IR spectra were recorded on a Perldn-EbQer Spectnim 1000 FT-IR spsctrophotometet. lonspray mass spectrometry (MS) spectra "wrae obtained on a Perldn-Ebner API 150EX mass spectrometer. Accurate mass measurements were performed on a Microms LCT dual probe. Preparative HPLC/MS was performed on a "Waters/Micromass Platform ZQ system equipped witii System A: ACE 5 C8 colunm (19x50nmi), eluents: MilliQ water, MeCN and MiUiQAieCN/0.1%TFA and systemB: XterraMS CIS, 5fim column (19x50mm), eluents: MilliQ water, MeCN and NH4HCO3 (lOOmM). Analytical HPLC were perfoimed OD Agilent 1100, colunm: ACE 3 CS (system A) or column: YMC-Pack (system B), eluents; IvfilliQ/0.1 %TFA and MeCN. Elemental analyses wra-e performed on a Vario El instrument. Preparative flash chromatography was performed on Merck sQica gel 60 (230-400 mesh). Legend fo Scheme 1: i) Hydrogen gas, Pd/C, Meflianol; ii) Sodium nitrite, Sutiric acid, diverse thiols (R'-SH), OK iii) meta-cMorq>eroxybenzoic add (ni-CPBA), dichloromefliane (CHjCli), overnight; iv) phosphorus oxyloMoride (POClj), acetonitrile (CH3CN), 80 "C, 2h; v) aliphatic cyclic amines (R), SO °C, CH;CN; vi) Ha in diefiiyl ediei. Methods The assigned structures were oonfiiroed by standard spectrascopical methods and elemental analysis and/or high resolution MS. NMR spectra were obtained on Bmker 500 MHz or JEOL 270 MHz spectrometer at 25'C, and the chemical shift values are reported as parts per million (S). MS spectra were acquired on a 2690 Separation Module (Watt's) with a Platform LCZ (Micromass). Flash chromatography was performed on Silica gel 60 (Merck) or LiChroprep RP-18 (Merck). HPLC analysis were accomplied on a HP Series II00, with a GROM-SIL 100 ODS-0 AB column, 4.6x50mm. The HPLC puriBcaticms were performed on preparative HPLC/ Mass system using YMC Combi prep ODS-AQ column, 56x20 mm, Gilson pumps, Dynamax U\'-l detector and Fimiigan Mass detector. The used eluaits were H2O and CH3CN, bo with 0.1% TFA. The purity of fee confounds was determined by HPLC. Elemental analysis was perfbnned at Structural Chemistry Department, Eiovitrum AB, Stockiiolm. Melting points, when given, were obtained on a Buchi or a Gallenkamp melting point paratus and are uncorrected. INTERMEDIATE 1 Synthesis of 6-Aimno-iiiiinDline A suspension of 6-mtro-quinoline (8.7 g, 5 mmol), palladium on charcoal (10 %) (0.1 g) in meflianol (0,2 L) was hydrogenated at room temperature for 24 with stirring. The catalyst was filtered and the solvent evaporated to yield a yellow solid. Crystallisation fi:oni ethyl acetate yielded the pure title compound as a pale yellow sohd (3.3 g, 46 %). MS m/z: 145 [M+H+]. 'H NMR (270MHz, CHCb-d) 5 ppm 3.89 (s, 2 H) 6.87 (d, J=2.64 Hz, 1 H) 7,14 (dd, >8.97,2.64 Hz, 1 H) 7.25 (dd, /=8.44,4.22 Hz, 1 H) 7.88 (dd, /=7.92, 1.58 Hz, 1 H) 7,90 (d, J=8.97 Hz, 1 H) 8.63 (dd,.=4,22,1.58 Hz, 1 H). ESITERMEDIATE 2 Synthesis of 6-phenylsiilfanyl-quinoline A solution of sodium nitrite (1 g, 14 mmol) in water (6 mL) was slowly added to a stirred solution of 6-amino-quinoIine (1,44 g, 10 mmol) in snlfimc acid (50 %) (8 mL). The temperature w kept below 5 "C during the additice. The reaction mixture was poured into a solution of potassium hydroxide (9 g, 16mmol)andthiophenoi(lmL, 9 nuno!) in water (30 UiL). The reaction mixture was refluxed for 3 h, cooled and extracted with diethyl efliEj. The insoluble material was eliminated by filtration. During filtration most of the material was trapped in the sohd phase. The filtrate was evorated and the residue was purified by column chromatogrhy (Si02, ethyl acetate:hexan.e, 1:2) to yield a colorless oU (100 mg, 4% PS: the bw yield is due to the loss of &e material during the filtration procedure). MS m/z: 238 [M+H+]. 'HNMR (270 MHz, CDjCl) 5 ppm 7.34 (m, 4 H) 7.42 (m, 2 H) 7.57 (dd, /=8.97,2.11 Hz, 1 H) 7.67 (d, >2,11 Hz, 1 H) 7.99 (m, 2 H) 8.84 (dd, ..22,1.58 Hz, IH). INTERMEDIATES Synthesis of 6-benzenesulfonyl-qiunoline 1-oxid A solution of m-chloroperbenzoic acid (1 g, 5.8 nnnol) in DCM (10 roL) was added to a stiiTed solution of 6-phenylsiilfiinyl-qmnolirie (0.25 g, 1 mmol) andNaHCO3(0.5 g)in DCM (10 mL). The reaction was left stiniag overnight, washed with water, NaHCOa solution and evEqrorated. Trituration of the residue in diethyl ether gave the pure title product as a slightly yellow solid (0.14 g, 30 %). MS m/z: 287 [M+H+]. INTERMEDIATE 4 Synthesis of 6-benzenesnIfonyI-4-cliloro-niiioliDe A solution of 6-beozenesulfonyl-quinoline 1-oxid (135 mg, 0.47 mmol) in POCI3 (4 mL) was heated at 90 °C for 2 h after which the solution was poured on ice, ammonium hydroxide was added and extraction with DCM. The organic phase was dried (NaS04), the volatiles were evaporated and flie residue was purified by column chromatography (Si02, ethyl acetate:petroleum ether, 1:1) to yield a white solid (39 mg, 27 %). MS m/z: 305 [M+H+]. EXAMPLE 1 Synthesis of 6-benzenesuIfonyI-4-piperazin-l-yl-qninoliBe hydrochloride A solutioa of 6-benzKiesulfonyl-4-chloro-quinoline (35 mg, 0.11 mmol) and piperazine (0.5 g, 2.5 mmol) in acetonitrile (2 mL) was heated at SO °C over night. The mixture was extracted wifli toluene and water. The organic phase was purified by chromatography on sihca gel eluted with CHCU saturated with NHj (gas). The pure product was dissolved in ethyl acetate and HCI (gas) in diefliyl ether was added. The resulting oily residue was dissolved in methanol and ethyl acetate and evorated to yield a white solid (24 mg, 77%). MS m/z: 354 [M+H+]. 'H NMR (270 MHz, CH3OH-D4) 5 ppm 3.52 (m, 4 H) 4,13 (m, 4 H> 7.36 (d, 7.18 m, 1H) 7.57 (m, 3 H) 8.01 (m,>U.25,8.54 Hz, 3 H) 8.2S (d, JKSl Hz, I H) S.63 (d, .68 Hz, 3 H) 8.69 (s, 1 H). Legend for Scbeme 2: i) NaffluO, Pd(PPti3)4, n-BuOH, BOC-protected diamines; ii) terf-butyl piperazine-!-oaiboxylate or /ert-butyl 1,4-diflzepane-l-caibojQ'late, trietliylarQine or KjCOj, DMSO, thiols; iv) TFA, H/)3, NaOH; iv) HCL I Method A Preparation of tbiol derivatives tert-Butyl 4-(6-bromoqiimolm-4-yl)-l,4-diazepane-l-carboxylate (0.5 g, 1.23 mmol) was mixed with the thiol (1 equiv.), NaOfflu (2 equiv.), Pd(PPh3)4 (0.05 equiv.) and n-BuOH {5 mL) in a reaction tube. N2 (g) was flushed flirough flie mixture for 30 minutes. The reaction ' mixture was heated to 120°C overnight The precipitate was filtrated and the reaction mixture conccinttated in vacuo. The Tesadue was dissolved in EtO Ac and washed wi'Gi H3O, dried (MgS04) and evaporated. Purification by flash chromatogjhy using DCM: MeOH 98;2 as elueait afforded the title product that was used in the nect step without farther purification. Me&odB Oridstion of thiol derivatives to sulphone derivatives The appropriate thiophenoJs derivatives aie dissolved in TFA (5 mL) and stirred for 15 minutes at room temperature. H2O2 (2 mL) was added and the reaction was left stirring overnight. The reaction mixtures are evEorated and the residues are portioned between diethyl eflier and water. The layers are separated and the water layer is extracted with dietiiyl ether and made basic by adding NaOH IM. Extraction with DCM, drying with MgS04 and evaporationves &e free bases of fee pixducts which are dissolved in EXAMPLE 3 6-(l-NaphthyIsnIfonyI)-4-piperazin-l-y!qninoliiiebydrochIoR1de A total amount of 2.25 mnaol, of the ipropR1ate thiophenol was used and the reaction was prolonged with 8 hours. The oxidation step was completed after 24 hours at ambient temperature. PuR1fication by column cbroniatography on silica gel 10-20 % MeOH in DCM gave the &ee amine fliat was converted to the HCl-salt. Yield 14 mg (4 %). Grey solid. HPLC 95%, RT=.54 (System Al, 10-97% MeCN over 3 min). H NMR (400 MHz, DMSO-de) 6 ppm 3.33 (s, 4 H) 4.06 (s, 4 H) 7.38 (d, .=6.78 Hz, 1H) 7.65 (d, J=7.53 Hz, 1 H) 7.69-7.75 (m, 1 H) 7.82 (t,7.78 Hz, 1 H) 8.12 (d, 8.03 Hz, 1 H) 8.21-8.30 (m, 2 H) 8:38 (d, 8.03 Hz, 1H) 8.56 (t,8.53 Hz, 2 H) 8.74-8.79 (m, 2H) 10.05 (s, 2 H). MS (ESI+) for C23H21N3O2S m/z404.4 (M+H HEMS for C23H2!N302S: calcd, 403.1354; found, 403.1365. EXAMPLE 4 6-[(3,4-DichIoropbeDyl)sii]fonyl]-4-plperaziii-lyIqQmoIiiie hydrochloR1de A total amount of 2.25 mmol of &e appropR1ate thiophenol was used and the reaction was prolonged with 8 hours. The oxidation step was completed after 24 hours at ambient temperature. PuR1fication by column chromatography on silica gei 10-20 % MeOH in DCM gave the fiee amine which was converted to the HCl-salt giving yellow solid. Yield 15 mg (3 %. Yellow soUd., HNMR(400 MHz,DMSO- de) 5ppm 3.35-3.41 (m, 4H) 4.06-4.15 (m, 4 H) 7.40 (d, 6.78 Hz, 1 H) 7.93 (d, /=8.53 Hz, 1H) 8.04 (dd, J-8.53, 2.01 Hz, 1 H) 8.27 (d,7=9.03 Hz, 1 H) 8.32 (d, 2.01 Hz, 1 H) 8.36-8.42 (m, 1 H) 8,73 (d, J=1.51 Hz, 1H) 8.82 (d, 7=6.53 Hz, 1 H) 9.86 (s, 2 H). MS (ESI+) for C19 Hn Cb Nj O2 S TTi/z422.2 (M+H. HRMS forC19H,7Cl2N302S: caJcd, 421.0419; found, 421.0422. HPLC 95%, R-r=2.69 (System Al, 10-97 % MeCN over 3 min) EXAMPLES 6-[(3-Dimetliylphenyl)salfonyll-4-piperazin-l-ylqninoline hydrochloR1de The oxidation step was completed after 2 hours at ambient temprature. PuR1fication by column chromatography on silica gel 10-20 % MeOH in DCM gave the free amine which was converted to the HCl-salt giving grey solid. Yield 0.007 g (2 %). Yellow sohd. HPLC 90 %, RT=2.57 (System Al, 10-97 % MeCN over 3 min). MS (1+) for C21H23FN3O2S m/z 382.2. HRMS for C1HjsFNsCbS: calcd, 381.1511; found, 381.1521. EXAMPLE 6 6-[(2-Cbloro-6-inethyIphenyI)snlfoDyl]-4-piperazin-l-ylquiDOliBe hydrochloR1de A total amount of 2.25 mmol, of the propR1atethiophenol was used and the reaction was prolonged with 8 hours. Additional H2O2 (1 mL) was added and the reaction mixture was stirred at 50 °C for another 48 hours. PuR1fication by column chroroatogrhy on silica gel 10-20 % MeOH in DCM gave the &ee amme (hat was converted to the HCl-salt Yield 3 3 mg (7.5 %). White soHd. HNMR(400MHz,DMSO-d) Sppm2.13 (s, 3 H) 2.98 (s, 4H) 3.72 (s, 4 K) 7.06(0, J=6.7& Hz, I H) 7.14 (dd, -11.54, 8.03 Hz, 2 H) 7.23 (t 7.78 Hz, 1 H) 7.89 (d, y=8.78 Hz, 1 H) 7.94-8.00 (m, I H) 8.24 (s, 1 H) 8.45 (d, J=6.78 Hz, 1 H) 9.68 (s, 2 H). MS {ESI+) for CjoHjoC1NsOiS m/z 402.2 (M+H. HRMS for CaoHjoClNjOjS: calcd, 401.965; found, 401.967. HPLC 95 %, R1=2.55 (System Al, 10-97 % MeCN ovCT 3 min). EXAMPI£7 6-[(4-Chlorophenyl)snIfonyl]-4-piperazin-I-yIquinoUBe hydrochloR1de A total amount of 2.25 mmol, of the appropR1ate thiophenol was used and the reaction was prolonged for another 8 hours. The oxidation step was completed after 24 h at ambient temperature. PuR1fication by colunm chromatography on silica ge! 10-20 % MeOH in DCM gave the free amine that was converted to the HCl-salt Yield 14 mg (3 %). Yellow solid. HPLC 95 %, RT=2.66 (System Al, 10-97 % MeCN over 3 min). MS (ESI+) for C19Hi8C!N302S m/z 388.2 (M+H. HEMS for C19H,sClN302S: calcd, 387.0808; found, 387.0821. EXAMPLES 6-[(2-Methyl,4-tert-bntyl-phenyI)sulfonyi]-4-piperazu)-l-ylqumoIiQe hydrochloR1de The oxidation step was completed after 2 hours at ambient temperature. PuR1fication by column chromatography on silica ge! 10-20 % MeOH in DCM gave the fl:ee amine which was converted to the HCl-salt giving gray solid. Yield 17 mg (4 %). HPLC 95 %, R1=2.81 (Sysfen Ai, 10-97 % MeCH over 3 min). MS (ESI+) for Ca4H2eN302S m/z 424.2 (M+}t). HRMS for C24H29N3O2S; calcd, 423.19S0; found, 423.1969. EXAMPLE 9 6-[(3D!iiiethylpheDyl)sulfonyI]-4-piperaaan-i-ylquuioUne hydrochloR1de The oxidation step was completed aftar 2 hours at ambient temperature. PuR1fication by column chromatogr£5)hy on sihca gel 10-20 % MeOH in DCM gave the &ee amine which was converted to the HCl-salt. Yidd 33 mg (8 %). Yellow solid. H NMR (400 MHz, DMSO- ds) 5 ppm2.27 (d,.6.27Hz, 6H) 3.34 (s, 4H)4.12 (s, 4H) 7.39 (dd, 7.40, 2.13 Hz, 2 H) 7.75 (d, 7.78 Hz, 1 H) 7.81 (s, 1 H) 8.32 (s, 2 H) 8.61 (s, 1 H) 8.78 (d, 6.78 Hz, 1 H) 10.18 (s, 2 H). MS (ESI+) for C2]H23N302S m/z 382,2 (M+H. HEMS for C21H23N3O2S: calcd, 381.1511; found, 381.1519. HPLC 95 %, RT=2.54 (System A1, 10-97 % MeCN over 3 min). EXAMP1£10 6-[(23-DichIorophenyl)salfoQyI}-4-piperazin-l-ylqiilaoUne hydrochloR1de A total amount of 2.25 mmol, of the appropR1ate thiophenol was used and the reaction was prolonged for another 8 homs. The oxidartion step was completed after 24 hours at ambient temperature. PuR1fication hy column chromatography on silica gel 10-20% MeOH in DCM gave the fre amine which was converted to the HCl-sait. Yield 15 mg (3 %). Yellow solid. HNMR (400 MHz, DMSO-dfi) 5 ppm 3.36 (m, 4 H) 4.10 (m, 4 H) 7.42 (d, 5.78 Hz, 1 H) 7.75 (t,8.03 Hz, ] H 8.07(4=8.03 Hz, lH)8.24(d,.04Hz, 1 H)S.33 (dd, 13.93, 8.41 Hz, 2 H) 8.70 (s, 1 H) 8.82 (d, J=6.78 Hz, 1 H) 10.00 (s, 2 H). MS (ESI+) for CSHITC1SNJOSS m/z Mil (M+H*). HRMS for C,9Hna2N302S: calcd, 421.0419; found, 421.0408. HPLC 95 %, RT=a.50 (System Al, 10-97 % MeCN over 3 min). EXAMPLE 11 6-[(4-tert-ButylphenyI)snlfonyll-4-piperazm-l-ylquinoUne hydrochloR1de tert-Butyl 4- {6-[(4-tert-butyheny])thio]quinolin-4-yl)piperaziiie-l-caiboxylate (0.60 g, 1.3 mmol) was dissolved in TEA (12 mL) and stirred for 30 minute before HaO: (0.65 mL, 6.3 mmol) was added. The mixture was stirred for 2 hours and water (5 mL) was added. The mixhire was evorated and the residue was taken up in water and washed with diefliyl eJher (2x). The aqueous pliase was adjusted to pH 10 with 1N NaOH and the mixture was extracted with CH2C12 (2x), dR1ed (MgS04) and evaporated. The residue was diluted with CHiCh and 1.3 mL 2N HC1 in diethyl ether was added under vigorous stirR1ng and flie mixture was evaporated and washed with diethyl ether (2 x) and dR1ed.Yield: 0.40 g (69 %). Grey solid. HPLC 95 %, Rr=2.77 (System Al, 10-97 % MeCN over 3 min). H NMR (400MHz, DMSO-de) 6 ppm 1.23 (s, 9 H) 3.3S (s, 4 H) 4.0S (s, 4 H) 7.39 (d, J=7.03 Hz, 1 H) 7.65 (d, J=8.53 Hz, 2 H) 7.96 (d, =8.53 Hz. 2 H) 8.25 (d, 8.78 Hz, 1 H) 8.30-S.36 (m, 1 H) 8.66 (d,.1.76 Hz, 1 H) 8,81 (d,7.03 Hz, 1H) 9.85 (br. s, 2 H), MS (ESI+) for C23H27N3O2S m/z 410.4 (M+H*). EXAMPLE 12 6-[(4-IsopropylpIieiiyl)siilfonyIJ-4-piperaziD-l-yIqiiibioline hydrochloR1de 4-Isopropyltbiophenol (0.152 g, 1.0 mmol) was aAied dropwise to a suspension oiiert-butyi 4-(6-bromo-quinolin-4-yl)-piperazine-l-carfaoxyIate (0.2 g, 0.51 mmol), Na-t-tmtoxide (0.192 g, 2.0 imno]) and Pd[P(Ph)3]-i (0.030 g, 0.025 mmol) in ethanol (3 raL) at 90°C and the mixture was stirred for 18 h. The mixture was diluted with THF and filtered through a plug of silica and eviorated, The crude product was dissolved m TFA (5 ruL) and stined for 15 mintrtes before 30 % H2O2 (1 mL) was added. The mixture was stirred for 2 hours and evqiorated. The residue was dissolved in water and washed with CH2C12 (2x) and 2 N NaOH was added uniil pH reached 10 and the mixture was extracted with CH2C12 (3x), dR1ed (MgS04) and evaporated. The crude product was puR1fied by preparative HPLC 5-95 wata-/acetonitR1le collectu on m/z 395.2. After evaporation the free amine was dissolved in CH2C12 and and excess of HC1 in diethyl ether was added and the mixture was evrorated. Yield 0.015 g (7 %). H KMR (400 MHz, DMSO-da) 5 ppm 1.17 (d,7.03 Hz, 6 H) 2.90-3.02 (m, 1H) 3.34-3.42 (m, 4 H) 4.03-4.12 (m, 4 H) 7.39 (d, 6.7S Hz, 1 H) 7.51 (d, 8.28 Hz, 2 H) 7.96 (d, 8.53 Hz, 2 H) 8.26 (d, J=9.03 Hz, 1 H) 8.29-8.36 (m, 1 H) 8.66 (s, 1 H) 8.80 (d, 6.78 Hz, 1 H) 9.85-9.97 (m, 2 H). HPLC 95%, RT=2.65 (Sjtan Al, 10-97% MeCN over 3 min). EXAMPLE 13 4-Piperazin-l-yl-6-{I4-(tR1flHoroiiiefliyI)p]ienyl]snIfonyl}quinoline hydrochloR1de 4-TR1fiiioromethylfliicheiiol (0.178 g, 1.0 mmol) -was added drcwise to a suspension of tert-butyl 4-(6-bromo-quiiiolin-4-yl)-pipera2me-l-carboxylate (0.2 g, 0.51 nunol), Sodium-t-butoxide (0.192 g, 2.0 mmol) and Pd[P(Ph)3]4 (0.030 g, 0.025 mmol) in ethane! (3 mL) at 90°C and flie mixture was stiired for 18h. The mixture was diluted wifii THF and filtered through a plug of silica and evirated. The crude product was dissolved in TFA (5 mL) and stirred for 15 minutes before 30 % H2O2 (1 mL) was added. The mixture was s&red for 2 hours and evaporated. The residue was dissolved in water and washed with CH2C12 (2x) and 2 N NaOH was added until pH reached 10 and the mixture was extracted with CHjCb (3x) dR1ed (MgS04) and evorated The crude was puR1fied by preparative HPLC 5-95 water/acetonitR1le collecting on m/z 421.1. After evxratioE the &ee amine was dissolved in CH2C12 and excess of HCl in diethyl eliier was added and the mixture was ev£5)orated. Yield 0.024 g (10%). H NMR (400 MHz, DMSO-ds) 6 ppm 3.33-3.40 (ro, 4 H) 4.13-4.21 (m, 4 H) 7.42 (d, 7.03 Hz, 1 H) 8.02 (d, J-8.53 Hz, 2 H) 8.25-8.35 (m, 3 H) 8J7-8.53 (m, 1 H) S.76 (d,l.76 Hz, 1 H) 8.80 (d, J=7,03 Hz, 1 H) 9.95-10.O5 (m, 2 H). Yellow oil. HPLC 95 %, RT=2.66 (System Al, 10-97% MeCN over 3 min). INTmMEDIATE6 tert-B«tyl4-(6-broinoqniiiolin-4-yI)-l,4-diazepaHe-l-carboxyIate 6-Bromo4-cbloroquinoIine (3.5 g, 14.5 mmol) was reacted with fert-butyl lj4-diazepane-1-caiboxyiate (3.7 g, 18.8 mmol) and K2CO3 (4 g, 29 mmol) in DMSO at 100 X ovemigbt. After cooling the mixture was poured into wata- and extracted with DCM. The organic layer was washed with Wats, dR1ed (MgS04) and evorated. Tbe residue was puR1fied by flash chromatogrhyusing a gradient of EtOAc:hexane 1:1 to 2:1 giving 2.1 g (36 %) of yellow oil. H NMR (400 MHz, CDC13) 5 ppm 1.47 (d, 5.5 Hz, 9 H) 2.08-2.16 (m, 2 H) 3.35-3.44 (zn, 4 H) 3,60-3-73 (m, 4 H) 6.87 (d, 5.5 Hz, 1 H) 7.69 (dd, 9.0, 2.0 Hz, 1H) 7.88 (4 -S-5 Hz. 1 H) 8.16 (s, 1 H) 8.65 (d, 5.0 Hz, 1 H). MS (ESI+) for C19H24BrN30a m/z 406.4 (M+H) HRMS (EI) calcd for C19H24BrN3: 405.1052, found 405.1045. INTERMEDIATE 7 tert-Butyl-4{3-[(4-tert-bntylpheny0tliiolquiBolm-S-yIH.4-diazane-l-carboxylatB (General Method A) ThecompoiiDdwasprepaiedfix)mtei:t-hityi4 INTERMEDIATES tert-BHtyI-4{3-{(4-isopropylphenyr)lhio]qniiiolia-5-yI}-l,4-dia2epane-l-carbosy1ate (General Method A) The compound was prepared from tert-butyt 4-(6-bromoquin.Q!in-4yIl,4-diazane-l-carboxylate (0.5 g, 1.23 ramol) and 4-isopropylbenzeQethiol (0.19 g, 1.23 HUQOI). Yield: 0.27 g (46 %) of -tbe title coropoimd that WEB iised in iht next step -without fiirther puR1fication.HPIX89%,RT: 3.67min(5-99%MeCNcontaimng0.1 %TFAover3 mm); MS (ES1+) for C2BH3SN302S m/z 47S.2 (M+H)"". EXAMPLE 14 6-[(4-tcrt-But)lpheny])saIfoDyl]~4-(l,4-diazepaii-l-yI)quinoIine hydrochloR1de (General Method S) The compound was synthesized from tert-butyl-4 {3-[(4-tert-butylphenyl)thio]quinolin-5-yIi-l,4-diazepaiie-]-carboxylate (0.27 g, 0.55 mmol). Yield: 20 mg (8 %) of the title compound.; H NMR(27Q MHz, DMSO-de) S ppm 1.25 (a, 9H) 2.31 OTS,2H) 3.25 (brs,2H 3.49 (brs,2H)4.Ubts,2H) 4.26 (bis,2H7.16(d, J=7.1 Hz, 1 H) 7.65 (d, -=8.2 Hz, 2 K) 7.94 (d, J.2 Hz, 2 H) 8.19 (d, J=%.1 Hz, 1 H) S.26 (d, 7=8.7 1 H) 8.62 (d, J=6.3 Hz, 1 H) 8.75 (s, \ H) 9.65 (br s, 2 H); MS (ESI+) for C24H29N3O2S m/z 424.2 (M+H)\ HPLC 93%, RT: 2.79 min (5-99 % MeCN over 3 min). EXAMPLE 15 4-(ly4-Diazepaii-l-yi6-[(4-isopropj1phenyI)siilfonyIIqniDoliDe hydrochloR1de (General Method B) The compound was prepared from t6rt-Eutyl4{3-[(4-isopropyIpheayl)thio]quinoIin-5-yl}-t,4-diazepaiie-l-carboxylate (0.27 g, 0,S7nunal). Yield: 15 mg(6 %) of 1iie title compound.; HNMR (270MHz,DMSO-de)Sppm 1.16 (d,..9Hz, 6H)2.31 (br s, 2H) 2.96 (m, 1 H) 3.25 (br s, 2 H) 3.49 (br a, 2 H) 4.11 (br s, 2 H) 4.26 (br s, 2 H) 7.16 (d, J=6.9 Hz, 1 H) 7.51 (d, J=S.2 Hz, 2 H) 7.94 (d, J=8.2 Hz, 2 H) 8.18 (d, J=B.7 Hz, 1H) 8.30 (d, 8.4 Hz, 1 H) 8.62 (d, 6.I Hz, 1 H) 8.75 (s, 1 H) 9.62 (br s, 2 H); MS (ESI+) for C2JH27N3O2S m/z 410.4 (M+H)*. HPLC 93 %, RT: 2.70 min (5-99 % MeCN over 3 min). Legend to Scheme 3: i) POa,; ii) KjCO), DMF, BOC-diammes; iii) Nat-BuO, aiiopheaiols, Pd(PPlfe)4; n-BuOH; iv) TFA, HjOj; v) HQ in diethyl eflier. INTERMEDIATE 9 T-Bromo-l-Cliloroisoqnmoyne To phosphorus oxychloR1de (46.6 mL, 0.5 mol) at room temperature was added, portionwise, 7-bromo-l-hydroxyisoqiuiioline (11.2 g, 0.05 mol). The mixture was heated to 100 °C for 90 min with R1d stirR1iig. On cooling to room temperature, the mixture was poured, cautiously onto ice/water (200 mL). Dropwise addition of aqueous ammonia raised the pH=8 and the resulting preC1pitate was collected by filtration, washing with cold water. The solid was dR1ed under reduced vacuum at 45 °C for 12 h. 13.86 g (115 %) Beige solid isolated, H NMR (DMSO-de) 6 8.4 (s, 1 H), 8.34-8.38 (d, J = 6 Hz, 1 H), 8.03-8.07 (m, 2 H), 7.91-7.96 (d, J = 6Hz, 1 H); HPLC: 96%; LCMS: 242,2446. Nudeopliilic displacement of ChloR1ne INTERlvIEDIATE 10 4-(7-Bromo-tsoqiilnoIine-I-yl)-piperazine-l-CarbosyIic aC1d, tert-hutyi ester To a suspsision of 7-bromo-l-cMoroisoqmnoline (3.14 g, 1 3 mmol) in DMSO (20 mL) at room temperature was added either caiboxylic aC1d tert-butyl (BOC)piperazine (7.23 g, 38.8 mmol) or BOC-homopiperazine (7.77 g, 38.8 mmol) and flienpotassium carbonate (5.36 g, 39 mmol). The mixture was heated to 110 "C for 24 b. On cooling, the mixture was poured onto icwat- (50 mL) and extracted with ethyl acetate (3 x 50 mL). The combined organic phases were washed with water 50 roL) and biine (50 mL). Before drying over anhydrous sodium sulfate. Removal of solvent under reduced pressure gave crude product PuR1fication was performed by applying ihe crude mateR1al to a plug of silica in a filter funnel and eluting with heptane/ethyl acetate (2:1) and gave 2.73 g (54 %) yellow oil. H NMR (CDC1O 8 8.20-8.22 (m, 1 H), 8.13-8.1S (d, /= 6 Hz, 1 H), 7.65-7-71 (dd, J= 12, 3 Hz, 1 H), 7.59-7.65 (d, J= 12 Hz, 1 H), 7.21-7.25 (m, 1H), 3.64-3.73 (m, 4 H), 7.27-736 (m, 4 H), 1.49 (s, 9 H); LCMS: 392,394,395. INTERMEDLTEll 4-(7-Bromo-isoqttmQlise-l-yl-[l»41diazepaEe-l-ca,rljoxyIic aC1d, tert-butyl ester 2.75 g (52 %) yellow oil isolated HNMR (CDCb) 6 8.19-8.24 (m, 1 H), 8.06-8.12 (d, J= 9 Hz, 1 H), 7.54-7.68 (m, 2 H), 7.U (m, 1 H), 3.47-3.74 (m, 8 H), 1.98-2.16 (m, 2 H), 1.48 (s, 9 H); LCMS: 406,407,408. Palladium-catalysed aryl thiol coupling To 7-bromo-l-chloroisoquinoIine (1 mmol) in bufan-l-ol (20 mL) at room temperature was added sodium rert-butoxide (481 mg, 5 mmol), Ihiol (1.5 mmol) and tetralds tR1phecylphosphine paUadiiun (60 rag, catalytic). The mixture was heated to 120 °C for 16 h. On cooling to room temperature, the mixture was filtered through silica elutk wi-fii THF. Removal of solvent under reduced pressure gave the crude product which was used ■without further puR1ficadon in the subsequait step. INTERMEDIATE 12 4-[7-(2-Chloro-6-iiiefliyl-plienylsnIfanyI)-isoqnmolin-l-yl]-piperaR1ne-l-carbosy!ic add ieff-batyl ester Amixture of 4~(7-broino-isoquinoline-l-yI)-pipgrazine-l-carboxi4ic aC1d, (ert-butyl ester (0.5 g, 1.3 mmol), 2-chloro-6-me&yl-fhiophenol (0.206 g, 1.3 mmol), NaSuO (0.44 g, 4.5 mmol), Pd(PPh3)4 (74 mg, 0.065 mmol) in nBuOH (10 mL) was heated at 110 "C, 3h. The reaction mixture was filtered. The filtrate was concentrated and die residue was dissolved in ethyl acetate. The oi;gaaic phase was washed wife water (50 mL x 3), separated and dR1ed gSOj), filtered The volatiles were evaporated and the residue was puR1fied by flash colinrm chromatography (Si02, n-heptane: ethyl acetate 8:2) to give 530 mg of the title confound as colourless oil (yield 86.4 %). H MMR (CDC13) S 8.05 (d, IH), 7.65 {d, IH), 7.20-7.45 (m, 5H), 7.15 (d, IH), 3.26-3.40 (m, 4H), 3.10-3.20 (m, 4H), 2.5 (s, 3H), 1.38 (s, 9H). INTERMEDIATE 13 4-[7-(2-butyl-pheBylsiilfaiiyi)-isoquinolin-l-yl]-piperae-l-carboxyUcaC1dtert-bnfyl ester A mixture of 4-(7-bronio-isoqiiinohne-l-y!)-pipera2ine-l-carboxylic aC1d, tert-hutyl ester (0.5 g, 1.3 mmoi), 2-r-butyl-ttiiDphMiol(0.216 g, 1.3 inmol),Na/-BuO (0.44 g, 4.5 mmoi), PdCPPhs)* (74 mg, 0.065 wmol) in n-BaOB (10 mL) was heated at 110 °C, 3h. Ihe reaction mixture was filtered. The filtrate WM concentrated and the residue was dissolved in ethyl acetate. The organic phase was washed with water (50 mL x 3), separated and dR1ed (MgS04), filtered. The volatile were evaporated and the residue was pmified by flash column chromatophy (SiOa, n-heptane: ethy! acetate 8:2) to give 440 mg of the title compound as colorless oH (yield 71 %). H NMR (CDC13) S 8.00-8.10 (m, 2H), 7.15- 7.65 (m, 7H), 3.60-3.70 (m, IH), 3.30-3.45 (m, 4H), 3.05-3.20 (m, 3H), 1.55 (s, 9H), 1.50 (s,9H). IrrBRMEDIATE 14 4-[7-(3,4-Dichloro-phCTyIsnIfanyr)-isoqoiQoliB-l-yI]-piperazme-I-carboxylic aC1d tert-butyl ester A mixture of4-(7--bromo-isoqumoliiie-l-yl)-piperazine-l-carboxylic aC1d, fert-butyl ester (0.5 g, 1,3 inmol), 3,4-dichloro-thiophenol (165 uL, 1.3 mmol), NarBuO (0.44 g, 4.5 mmol), Pa(PPh3)i (74 mg, 0.065 mmol) in n-BuOH (10 mL) was heated at 110 °C, 3h. The reaction mixture was filtered. The filtrate wsa concentrated and the residue was dissolved in eihyl acetate. The organic phase was washed with water (50 noL x 3), sarated and dR1ed (MgSO), filtered. Hie volatiles were evairorated and the residue was puR1fied by fiash column chromatograpby (SiOz, n-peatane:ethyl acetate 9.5:0.5-8:2) to give 230 mg of the title compound as cobrless oil (yield 36 %). H NMR (CDGI3) 5 8.10-8.20 (m, 2H), 7.90 (bs, IH), 7.65-7.75 (m, 2H), 7.10-7.55 (m, 3H), 3.50-3.65 (m, 4H), 3.20-3.30 (m, 4H), 1.50 (s, 9H). INTERMEDIATE 15 4-[7-{3,4-Dimetiiyl-phenyIsHlfanyO-isoqBliioliB-l-yl]-piperaziBe-l-carboxylic add lert-bntyl ester A mixture of 4-(7-bromo-isoquinoline-l-yl)-pip6raziQe-l-cai:boxylic aC1d, tert-hv&y\ ester (0.5 g, 1.3 mmol), 3,4-dimethyl-fiiophenol (175 uL, 1.3 mraol), Na/BuO (0.44 g, 4.5 mmol), Pd(PPh3)4 (74 mg, 0.065 mmol) in n-BuOH (10 mL) was heated at 110 °C, 3h. The reaction mixture was filtered. The filtrate was concentrated and the residue was dissolved in siayi acetate. The organic phase was washed with water (50 mL x 3), separated and dR1ed (MgSOi), filtered. The volatiles were evaporated and the residue was puR1fied by flash column chromatogrhy (SiCb, n-pentane:ethyl acetate 9.5:0.58:2) to give 260 mg of the title compound as colorless oil (yield 44 %). H NMR (CDCls) 5 8.00-8.10 (m, 2H), 7.55-7.65 (m, 3H), 7.40-7.50 (m, IH), 7.10-7.30 (m, 2H), 3.30-3.40 (m, 4H), 3.10-3.20 (m, 4H), 2.30 (s, 3H), 2.25 (s, 3H), 1.50 (s, 9H). INTERMEDIATE 16 4-[7-(3,S-Dimeaiyl-phenyIsnlfanylisoqBinoUn-l-yIl-piperaziiie-l-carboxylicaC1dfert-butyl ester A mixture of 4-(7-broino-isoqiiiiioline-l-yl)-pipe3-azane-l-cafboxy]ic aC1d, tert-hutyi ester (0.5 g, 1.3 nunol), 3,5-dimethyl-fliiophKiol (180 mg, 1.3 mmol), NauO (0.44 g, 4.5 mmol), Pd(PPh3)4 (74 mg, 0.065 mmoO in nBuOH{10 mL) was heated at 110 °C, 3h. The leacUoG mixtore was filtered. Tlie filtrate was conoetrfiated and ttie lesidae was dissohed in ethyi acetate. The orgaiio phase was washed with water (50 mL x 3), separated and dR1ed (MgSOi), filtered. The volatiles were evaporated and the residue was puR1fied by flash column chromato:aphy (Si02, n-pentane:ethyl acetate 9.8:0.2-»-8:2) to give 380 mg of tiie title conqmund as colourless oil (yield 65 %). H MMR (CDCb) 5 8.05-8.10 (m, IH), 7.80-7.85 (m. IH), 7.60-7.75 (m, IH), 7.17-7.25 (m, IH), 7.10 (bs, 2H), 7.00 (bs, IH), 3.40-3.50 (m, 4H), 3.10-3.20 (m, 4H), 2.25 (bs, 6H), 1.50 (s, 9H). I5TEaMEDIATE 17 4-[7-(/»-ChIoro-phenylsuIfanyl)-isoqiiiiioIiii-l-yl]-piperazme-l-carboxylic aC1d tert-bufyl ester Amixture of 4-(7-bromo-isoquinoline-I-yl)-piperazine-l-caiboxylic aC1d, rert-butyl ester (0.5 g, 1.3 mmol), ;7-chloro-thioplieiiol (188 mg, 1.3 mmol), Na/BuO (0.44 g, 4.5 mmol), Pd(PPh3)4 (74 mg, 0.065 mmol) ha nBuOH (10 mL) was heated at 110 "C, 3h. The reaction mixture was filtered. Tlie filtrate was concentrated and the residue was dissolved in ethyl acetate. The organic phase was washed wifii water (50 mL x 3), separated and dR1ed (MgSOfl), filtered. The volatiles were evaporated and the residue was piiR1fied by flash column chromatography (Si02, n-pentane:ethyl acetate 9.5:0.5 - 8:2) to give 300 mg of the title compound as colourless oil (yield 50 %). HNMR (CDC13) 5 8.05-8.15 (m, 2H), 7.60-7.70 (m, 2H), 7.40-7.50 (m, 2H), 7.15-7.30 (m, 3H), 3.45-3.55 (m, 4H), 3.10-3.15 (m, 4H), 1.50(s,9H). INTERMEDIATE 18 4-(7-PhenyIsuifanyl-isoqaInoliiie-l-j1)-piperazuie-l-carbosyIic aC1d, tert-butyl ester LCMS: 422,423, INTERMEDIATE 19 4-[7-(4-fert-Btttyi-pIieiiyIsiilfanyI)-isoqamoIiBe-l-yI]-piperazine-l-carboxylicaC1d, tert-huty\ ester LCMS: 478,479. INTERMEDIATE 20 4-(7-PheiiylsuIfanyl-isoqiunoline-l-yl)-[l,4]diazepane-l-carboKylic aC1d, tert-butyl ester MS: 368,369,370. INTERMEDIATE 21 4-t7-(4-to-(-Butyl-phenylsiiIfaiiyl)-isoq«inol!ne-l-yI]-[l,4Idiazepane-I-carboxylicaC1d, tert-bnty! ester MS: 424,425,426. INTERMEDIATE 22 4-[7-(2-ChIoro-6-methyl-phenyIsnlfaiiyisoq«iiioliiie-l-y!l-[l,4]diazepane-l-carboxyKc aC1d, tert-butyi ester MS: 416,417,418. INTERMEDIATE 23 4-[7-(3,4-DiincthyI-phenylsuIfanyI)-isoquinoiiiie-l-ylI-fl,4]diazepaiie-l-carboxylic aC1d, teii-batyl ester MS; 396,397,398. INTERMEDIATE 24 4-[7-(3,4-Dicliloro-pheDylsulfaiiyI)-isoqaino!ine-l-yl]-[l,4Idiazepaae-l-carboxync aC1d, Wrt-butyl ester MS: 436,437438. mTERMEDIATBlS 4-[7-(4-C!iIoro-pbenyIsuIfenyl)-!soqiiiBoliiie-l-yI]-[ly4}diazepane-l-carboxylieadd, ten-butyl ester MS: 402,404. INTERRffiDIATE 26 4-[7-(3,4-Dimettiyl-phenylsiilfanyIisoquiBoIine-l-yl]-[l,4]diazane-l-carbosyUc aC1d, tert-butyl ester LCMS: 464,465,466. INTERMEDIATE 27 4-[7-(2CTt-Butyl-phenylsiUfanyO-isoqnmoIine-l-yI]-[l,4IdiazepaBe-l-carboxyIicaC1d, /crt-bntyl ester LCMS: 492,493,494. BOC deprotection and oxidation of thiols to sutphone deR1vative Each thiol (0.2-1.14 mmol) was dissolved in tR1fluoroacetic aC1d (1.5 mL) at 0 °C and stirred for 15 mins at this tempCTature. To this was added 33% aqueous hydrogen peroxide solution (5-100 mL). The resulting mixture was stirred at room terrqierature for 90 min and then tTKited with sodium hydroxide solution (IM, 25 mL). Extraction of this mixture with ethyl acetate (3x50 mL) was followed by the washing of the combined organic layers with bR1ne (50mL). The organic extracts were dR1ed over anhydrous sodium sulfd:e and then the solvent was removed under reduced pressure. The crude product was puR1fied by preparativeLCMS. Treatment of the puR1fied mateR1al withHC1/Ether(lM, 1 mL)vethe final product as a white solid. EXAMPLE 16 7-(2-Chloro-6-metIiyl-beiizenesuIfoQyl)-l-piperaziB-l-yl-isoquiiioline hydrochloR1de A mixture of 4-[7-(2-chloro-6-raethyl-phenylsulfanyl)-isoquinolin-l-yi]-pipera2ine-l-caiboxyhc aC1d ferf-butyl estra" (160 mg, 0.340 mmol), H202 (30% in water, 200 uL), tR1fluoroacetic aC1d (2 mL) was heated at 50 °C, 2h. A water soliition of NaOH (IN) was added (pH = ] 4), ethyl acetate was added and the organic pktse was separated, dR1ed 0IgS04), filtered. The filtred was concaitrated and flie residue was puR1fied by flash column chromatogrhy (SiOi, dichloromefliane:methano! 8:2) to lead to 77 mg of the product compound as tee base (yield 56 %). Hie firee base was converted into hydrochloR1de by treatment with HCl in diethyl ether. H NMR (CHsOH-t/*) 5 8.S8 (bs, IE), 8.05-8.20(10. 3H), 7.65 (d, IH), 7.35-7.55 (m,3H), 5.85-3.95 (m,4H), 3.00-3.15 (m, 4H), 2.95 (s, 3H). EXAMPLE 17 7-(2-/-Bntyl~benzeiiesiiUbDyO-l-piperaziD-l-yl-isoqu{nol!ne hydrochloR1de A mixture of 4-[7-(2-Autylheny]suIfany!)-isoquino]m-l-yl]-piperazine-l-carboxylic aC1d /er/-butyl ester (273 mg, 0.571 mmol), H2O2 (30% in watCT, 1 mL), tR1fluoroacetic aC1d (3 mL) was heated at 50 °C, 2h. The reaction was continued oyemit at 35 °C. A water solution of NaOH (IN) was added (pE = 14), ethyl acetate was added and the organic phase was sarated, dR1ed (MgS04), fihered. TTie filtrated was concentrated and the residue was puR1fied by flash column chromatography (SiO;, dichloromethane:methanol 8:2) to le to 50 mg of flie title compound as fi-ee base (yield 56 %). The free base was converted mto hydrochloR1de by treatment with HCl in diethyl efli. H NMR (CHjOH-ct) 5 8.55 (d, IH), 8.25 (d, IE), 7.95-8.10 (m, 3H), 7.55 {d, IE), 7.55-7.65 (m, 2H). 7.4 (d, IE), 3.60-3.75 (m, 4H), 3.40-3.50 (m, 4H), 1.55 (s, 9H). EXAMPLE 18 7-(3,4-Dichloro-beiizenesiilfoDyI)-l-piperazin-l-y]-isoqiiiiioline hydrochloR1de Amixtuxeof4-[7-(3,4-dichloro-phenylsulfanyl)-isoquJnDlin-l-yl]-piperazme-l-carboxylic aC1d (ert-butyl ester (230 mg, 0.47 mmol), H2O2 (30% in water, 0.5 mL), tR1fluoroacetic aC1d (1.5 mL) was heated at 50 °C, 2h. The reaction was continued ovemit at 35 °C. A water solution of NaOH (IN) was added (pH = 14), efliyl acetate was added and the organic phase was separated, dR1ed (MgS04), filtered. The filtrated w concentrated and the residue was puR1fied by flash column chromatogrhy (SiCb, dichloromethanennethanol 9:1) The free base was converted into hydrochloR1de by treatment with HCl in diethyl eflier to otrtained 45 mg of the title conund. H NMR (CHsOH-d) 5 8.75-8.85 (m, IH), 8.10-8.30 (m, 4H), 7.90-8.00 (m, IH), 7.75-7.85 (m, IH), 7.50-7.60 (m, IH), 3.85-3.90 (ra, 4H), 3.50-3.70 (m, 4H). EXAMPLE 19 7-(3,4-Dimethyl-benzeDesulfonyI)-l-piperaziB-l-yl-isoqainoluiehydrocMoR1de A mixture of 4-[7-(3,4-dime1iiyl-phenylsulfanyl)-isoqiiinolin-l-yl]-piperaziiie-l-carboxylio aC1d tert-butyl ester (260 mg, 0.58 mmol), H2O1 (30% in water, 0.5 mL), tR1fiuoroacetic aC1d (1.5 mL) was heated at 50 "C, 2h. The reaction was continued overnight at 35 "C. A water solution of NaOH (IN) was added (pH = 14), ethyl acetate was added and fee organic phase was separated, dR1ed (MgS04), filtered. The filtrated was concentrated and the residue was puR1fied by flash column chromatography (Si02, dichlorometfiane:methanol 9:1) The fi-ee base was converted into hydrochloR1de by tteatmenl with HCl in diethyl eflier to obtained 20 mg of the title compound. H NMR (CR1OH-cL,) 5 8.75-8,80 (m, IH), 8.10-8.25 (m, 3H), 7.70-7.85 (m, 2H}, 7.60-7.70 (m, IH), 7,35-7.40 (m, IH), 3.9O-4.O0 (m, 4H), 3.55-3.65 (m, 4H), 2.35 (bs, 6H). EXAMPLE 20 7-(2,5-Dimethyl-beiizenesnIfonyl-pipera2in-l-yl-isoquinol!ne hydrochloR1de A mixture of 4-[7-(2,S-dimethyI-plieQyisulfanyl)-isoquinolin-l-yl]-piperazine-l-caiboxyIic aC1d iert-buiyl ester (380 mg, 0.846 mmol), H2O2 (30% in water, 0.5 mL), tR1fiuoroacetic aC1d (3 mL) was heated at 50 "C, 2h. The reaction was continued overnight at 35 °C. A water solution of NaOH (IN) was added (pH = 14), ethyl acetate was added and the organic phase was separated, dR1ed (MgS04), filtered. The filtrated was concentrated and the residue was puR1fied by flash column chromatogrhy (SiOi, dichloromethane:methanol 9.8:0.2-»9.5:0.5) The fi-ee base was converted into hydrochloR1de by treatment wifli HCl in diethyl ether to obtained 120 mg of iie title compound. H NMR (CHjOH-.) 5 8.75-S.80 (m, IH), 8.25-8.30 (m, IH), 8.05-8.20 (m, 2H), 7.60-7.70 (m, 3H), 7.30-7.35 (m, IH), 4.0O-4.1O (m, 4H), 3.60-3.70 (m, 4H), 2.30-1.35(bs,6H). EXAMPLE 21 7-(p-Chloro-beiizeDesnlfonyl)-l-piperaaB-l-yI-isoqiuBoIine hydrochloR1de Amixtureof4-[7-(p-cldoR1pheEylsulfen)d)-isoquinolm-l-yl]-piperazine-l-carboxylic aC1d leR1-hutyl ester (297 mg, 0.65 mmol), H2O2 (30% m wafer, 0.5 vaL), tR1fhioroaoetic aC1d (3 mL) was heated at 50 °C, Oh. The reaction was continued ovemi at 35 °C. A water solution of NaOH (IN) was added (pH = 14), ethyl acetate was added and the organic phase was separated, dR1ed (MgSOn), filtered. The filtrated w concentrated and the residue was puR1fied by flash column chromatography (SiOi, dichloromethanemelitanol 9.5:0.5~9.0;1.0) The free base was converted ioto hydrochloR1de by treatment with HC! in diethyl ethra to obtained 70 mg of flie title compound. H NMR (CHjOH-a!*) S 8.75-8.85 (m, 2H), 8.10-8.25 (m, 3H), 8.00-8.08 (m, 2H), 7.60-7.68 (m, 3H), 3.85-3.95 (m, 4H), 3.55-3.65 (m, 4H). EXAMPLE 22 7-BeiizeBesalfooyl-Jl-[l,4]diazepaD-l-yl-isoqumo!uie hydrochloR1de 30 mg. H KMR (DMSO-dtf) 5 9.3 (s, 1 H), 8,58 (s, 1 H), S.26-8.30 (d, J"- 9 Hz, 1 H), 8.1- 8.13 (m, 2 H), S.Ol-8.06 (d, 7= 6 Hz, I H), 7.6-7.76 (m, 3 H), 7.53-7.58 (d, /= 6 Hz, I H), 3.70-3.90 (m, 4H) 3.58-3.66 (m, 2 H), 3.29-3.40 (in, 2H); LCMS: 368,369 HPLC: 98 %. EXAMPLE 23 7-(4-tert-Butyl-benzenesulfonyl)-l-Il,41diazepan-l-yl]-isoquinoline hydrochloR1de Isolated 69 mg. HNMR (JMSO-de) 5 9.2 (s, 1 H), 8.65 (s, I H), 8.09-S.15 (d, J= 6 Hz, 1 H), 8.03-8.08 (d, J= 15 Hz, 1H), 7.89-7.96 (d, /= 9 Hz, 2 H), 7.60-7.67 (d, 7= 9 Hz, 2 H), 7,33-7.38 (d, J= 9 Hz, 1 H), 4.0M.09 (m, 2 H), 3.83-3.91 (m, 2 H), 3.43-3.52 (m, 2 H), 3.23-3.33 (m, 2 H), 1.25 (s, 9 H); LCMS: 424,425, HPLC: 97 %. EXAMPLE 24 7-(2-Chloro-6-methyI-benzenesnlfoDyr)-l-[l4]dia2epaii-i-yI]-isoqninoline hydrochloR1de Isolated27 mg HNMR(DMSO-d) S 8.81 (s, 1 H), 8.28 (m, 1 H), 8.10-8.18 (d,/=6Hz, 1 H), 7.94-8.08 (m, 2 H), 7.45-7.62 (m, 3 H), 7.36-7.42 (d, 7= 6 Hz, 1 H), 3.75-3.86 (m, 2 H). 3.41-3.51 (m, 2 H), 3.18-3.32 (m, 2 H), 2.86 (s, 3 H), 2.14-2.19(m 2 H); LCMS: 416,418HPLC:9S%. EXAMPLE 25 7-(33-Iu°ethyH)eiizenesitlfonyl)-l-[l,41diazepaii-l-yl]-isoqainoIiiiehydrocliloR1de Isolated 62 mg. H NMR (PMSO-ifs) 6 9.35 (s, 1 H), S.67 (m, 1 H), 8.00-8.18 (m, 3 H), 7.58-7.69 (m, 2 H), 7.45-7.41 (d, /= 6 Hz, 1 H), 7.30-7.35 (m, 1 H), 4.06-4.14 (m, 2 H), 3.86-3.97 (m, 2 H), 3.42-3.52 (m, 2 H), 3.23-3.31 (m, 2 H), 2.33 (s, 6 H) 2.23-2.25 (m 2 H); LCMS: 436,438, HPLC: 95 %. EXAMPLE 26 7-(3,4-Dichlor(-beiizeiiesiilfODyI)-l-[I,4]diazepaii-l-yl]-fSoqiunoIfne, hydrochloR1de Isolated 11 mg. HMvfR {CD3OD) 5 8.8S (m, 1H), 8.23-8.29 (d, J= 12Hz, IH), S.13-8.16 (d, y= 3 Hz, 1 H), 8.04-8.10 (d, /= 9 Hz, 1 H), 7.88-7.94 (d, /= 9 Hz, 1 H), 7.79-7.84 (d,/= 6Hz, 1 H, 7.67-7.73 (d,/= 9 Hz, 1H), 7.42-7.46 (d,/= 6H2,1H),4.2S-4.35 (m, 2 H), 4.09-4.16 (m, 2 H), 3.69-3.75 (m, 2 H), 2.33-2.45 (m, 2 H); LCMS: 368,369; HPLC: 97 %. EXAMPLE 27 7-(4-ChIoro-beiizenesnIfony[)-l-[l,41diazepan-l-yll-isoqiunoIine, hydrochloR1de Isolated 41 mg. HNMR (DMSCW5) 3 9.27 (s, 1 H), 8.68 (m, I H), 7.99-S.17 {m, 5 H), 7.66-7.75 (d, /= 9 Hz, 2 H), 7.33-7.39 (d, J= 6 Hz, 1 H), 4.03-4.U (m, 2 H), 3,83-3.93 (m, 2 H), 3.43-3.53 {m, 2 H). 3.23-3.32 (m, 2 H), 2.19-2.30 (m, 2 H); LCMS: 402,404; HPLC: 98 %. EXAMPLE 2S 7-{3,4-IimethyI-beQzeiiesuIfonyl)-l-[l,4]diazepan-l-ylj-isoqainoIme, hydrochloR1de Isolated 10 mg. H NMR (DMSatig) 5 9.41 (s, 1 H), 8.67 (s, 1 H), 8.00-8.16 (m, 3 H), 7.76-7.S2 (in, I H), 7.68-7.77 (d, 7= 9 Hz, 1 HJ, 7.32-7.42 (d, /= 9 Hz, 2 H), 3.99-4.40 Cm, 4 H), 3.49 (m, 2 H), 3.33 (m, 2 H), 2.29 (s, 3 H), 2.25 (s, 3 H); LCMS: 396,397; HPLC: 92%. EXAMPLE 29 7- Isolated 5 mg. H NMR (DMSO-ds) 5 9.27 (s, 1H), S.52 (s, I H), 8.06-8.16 (m, 2 H), 7.97-7.97 (rn, 2 H), 7.72-7.78 (m. 1 H), 7.61-7.70 (m, 1H), 7.40-7.45 (d, 7= 9 Hz, 2 H), 3.69-3.99 (m, 4 H), 3.43 (s, 2 H), 3.25 (s, 2 H), 2.05-2.26(iii, 2 H);1.52 (s, 9 H); LCMS: 424,425; HPLC: 90 %. EXAMPLE 30 7-Beitzenesiilfoityl-l-pipera-yI-isoqiiiBolme, hydrochloR1de Isolated 10 mg. H NMR pMSO-rffi) S 9.04 (s, 1 H), 8.65 (s, 1 H), 8.12-8.16 (d, /= 6 Hz, 1H), 7.98-8,05 (m, 5 H), 7.58-7.72 (m, 2 H), 7.32-7.36 (d, J= 6 Hz, 1 H), 3.98-4,04 (m, 4 H), 3.80-3.86 (m, 4 H); LCMS: 354,355; HPLC: 98 %. EXAMPLE 31 7-(4-teR1-Biityl-beiizeitesiiIfoByl-l-piperazm-yl-isoqumoIme, hydrochloR1de Isolated 10 rag. H NMR (DMSO-tf) 8 9.33 (s, 1 H), 8.57 (s, 1 H), 8.24-8.29 (d, J= 9 Hz, 1H), S.U (m, 2 H), 7.91-7.97 (d, J= 9 Hz, 2 H), 7.60-7.66 (d, J= 12 Hz, 2 H), 7.52-7.57 (d, y= 6 Hz. 1 H), 3.59-3.68 (m, 4 H), 3.29-3.40 (m, 4 H), 1.24 (s, 9 H); LCMS: 410,411 I HPLC: 90 %. I Legend to Scheme 4: (i) rert-bntyl 3-bydroxypyirolidinE-l-caifeoxylate or /ert-butyl4-liydroxypipeiiC1iiie-l-caiboxylate, PPI, DEAD, THF; (ii) HsCg), Pd/C, MeOH; (iii) R1-SOs-O, pyR1dme, CHaaz; (iv) HCl in diethyl eflier General method C Mitsonobia reaction of 4-nitro-l-Qb1hol with boc-protected 3-h.ydroxypyrroUdiiie and A-li3droxypjpeR1di23e 4-Nitro-l-nhfto] (1 eqmv.) was dissolved in THF (3 ml/mmol), len-butyl 3-bydroxypyrrolidiiLe-l-cafboxylate (2 equiv.) was added followed by PPhs (2 equiv,). The solution was kept under Ni-atmosphere and cooled with ice-bath. Diethylazodicarboxylate (DEAD; 2 equiv.) was added dropwise. The ice-bath was removed after 10 min and the reaction mixture was stirred at ambient teanperature overnight. The solvent was evorated and the residue was re-dissolved in EtOAc. The formed preC1pitate was collected by Sitration, The solution was concentrated in vacuo and puR1fied by flash chromatogrEhy {SiOi,EtOAc:so-hexane 2:8-EtOAc) General method D Reduction ofaitroBapbtbalene deR1vatives To a solution of coiresponding nitronaphthalenes (1 equiv.) (prepared by General method A) in MeOH (2 mL/nnnol), was added Pd/C (10%) and the reaction mixture was stirred ovemit under bydrogen (1 atm). The reaction mixture was filta and flie filtrate was concentrated in vacuo to ve corresponding aminonaphthalene deR1vafives. General method E IteacdoD of anuDonapbdialeiie deR1vatives wiih seaayl cliloR1des To a solution of the aminonaphftialette deR1vatives (1 equiv,) in CH2C12 (8 mL/mmol) was added pyR1dine (3 equiv.) followed by the corresponding sulfonyl chloR1de (1.2 equiv.). The mixtures were stirred at ambient temperature ovendghJ, washed with HCl (IM) (2 roL) and dR1ed (MgS04). The volatiles we eliminated under vacuo and gave die crude product which were puR1fied by flash chromatogrhy (SiOj, EtOAc:iso-bexane 1:4) to give desired sulfonamide. General method F Oeprotection of boc-gro&p The sulfonamide deR1vatives (prepared by General Method C) were dissolved in a small amount of MeOH and treated with an excess of HCl in diethyl ether (IM). StirR1ng at ambient temperature ovemit resulted in a preC1pitate which were collected by filtration giving the title compounds as its hydrochloR1de salte. General method G 3-HydroxypyiToJidine (lequzv.) was dissolved in MeOH (ImUmmoS) and cooled on ice-bath. (B0C)20 (1.1 equiv.) was added and the mixture was stirred for 2 h at ambient temperature. PyR1dine/water (10/1 OmL) was added and the mixture was stined overnight. Evaporation of solvents aad co-evaporation wift, toluene provided flie desired boc-protected 3-hydroxypyrroUdine. INTERMEDIATE 28 tert-Biil3-[(4-Ditr6-l-napIithyI)oxy]pyrrolidiiie-l-carboxy!ate fGenera/MeiAorfQ The crude product was puR1fied by column chromatogry. The compound was prepared from 4-nitro-l-nhl3ioI (2.85 g, 15.1 tmnol). The matmal thus obtained was dissolved in small amount of EtOAc and iro-hexane was added. The fomied solid was collected by filtration and tR1turated with MeOH to give the pure title confound 4.6g (85%). HPLC 99%, RT=2.70 (System Al. 10-97% MeCN over 3 min). H NMR (400 MHz, CDC13) 5 ppm 1.46 (d,=7.03 Hz, 9 H) 2.26-2.38 (m, 2 H) 3.60-3.81 (m, 4 H) 5.20 (br s, 1 H) 6.76 (d, 8.53 Hz, 1 H) 7.58 (t, 7.53 Hz, 1 H) 7.73 (t, 7.53 Hz, 1 H) 8.34 (dd, /=a0.33, 8.78 Hz, 2 H) 8.75 (d, J=9.04 Hz, 1 H). MS (ESH-) for C19H22N2O5 m/z 376.2 (M+NH)", 359.2 (M4H) 303.2 (M-iBu)*, HPLC99%, RT=2.78 min(SystemBl, 10-90% MeCN over 3 min). INTERMEDIATE 29 fert-Butyl 3-[(4-amino-l-BaphtiiyI)oxy]pyiToIidine-l-carboxylate (General Method D) The compound was pnared firom intermediate 1 (2.6 g, 7.2 mmol), Yield : 2.1g (87 %) of the title compound as puiple solid. HPLC 96 %, R-pl .768 min (System Al, 10-97 % MeCN over 3 min). HPLC 95 %, RT=1.604 min (Systran Bl, 10-90% MeCN over 3 min). H NMR (400 MHz, DMSO-de) 5ppm 1.37 (d, J=22.59 Hz, 9 H) 2.12 (s, 2 H) 3.43-3.46 (m, 4 H) 4.96 (s, 1 H) 5.50 (s, 2 H) 6.63 (d, J=8.03 Hz, 1 H) 6.81 (d,8.03 Hz, I H) 7.41 (dd, /=6.02,3.01 Hz, 2 H) 7.94-8.01 (m, 2 H). MS (ESI+) for C15H24N2O3 m/z 329.2 (M+H)*, 273.2 (M-rBu) 229.2 (M-Boc). INTERMEDLME 30 tert-Biityl3-[(4-{[(4-chIoropheByI)siilfonyllainmo}-I-oaphthyI)oxy]pyrroMitte-l-carboxylate (General method E) The compound was prepared from intermediate 2 (0.2 g, 0.61 mmol). The crade mateR1al was tR1turated wilii CH3CN to give 0.14 g (46 %) of &e title compound as apale pink solid. HPLC 97 %, RT=2.703 min (System Al, 10-97 % MeCN over 3 min). H NMR (400 MHz, CDC13) 5ppm 1.46 (d,4.02Hz, 9 H)2.1S-2.30 (m, 2H)3.54-3.76 (m, 4H) 5.05 (br s, 1 H) 6.62-6.65 (m, 1 H) 6.74-6.76 (m, 1 H) 7.17-7.23 (m, 1 H) 7.32 (d, /=9.04 Hz, 2 H) 7.39-7.45 (m, 2 H) 7.62 (d, S.53 Hz, 2 H) 7.68-7.72 (m, 1 H) 8.16-8.19 (m, 1 H). MS (ESI+) for C25H27C1N2O3S m/2 520.2 (M+NH4)*, 447.0 QA-iBaf. HPLC 98%, RT=2.738 min (System Bl, 10-90% MeCN over 3 man). INTERMEDIATE 31 (ef(-Bu The compound was prepared ftom intermediate 2 (0.2 g, 0.61 mmol). Yield: 0.2g (66%i) of file title compoimd as a pink oil. HPLC 98%, RT=2.617 min (System Al, 10-97% MeCN over 3 min).HNMR(400MHz, CDC1j) Sppm 1.45 (d,5.02Hz, 9 H) 2.14-2.31 (m, 2 H) 3.54-3.76 (m, 4 3.79 (s, 3 H) 5.04(br s, 1 H) 6.60-6.65 (m, 2 H) 6.81 (d, =8.53 Hz, 2 H) 7.15-7.24 (m, IH) 7.3S-7.44 (m, 2 H) 7.60-7.64 (m, 2 H) 7.71-7.76 (m, 1H) 8.14-S.18 (m, 1 H). MS (ESI+) for CjeHjoNjOeS m/z 516.4 (M+NH*)*, 443.0 (M-(Bu)", 399.2 (M-Boc)". INTERMEDIATE 32 /ert-Butyl3-I(4-{[(5-cliloro-2-tIiienyI)siiIfoayl]amino}-l[taphthyl)oxy]pyrroIidiiie-l-carboxylate (General method E) The compoimd was prepared ftom intermediate 2 (0.2 g, 0.61 mmol), Yield: 0.21g (68%) of the title compomid as ayellow solid. HPLC 99%, R1=2.777 min (SystemBl, 10-90% MeCN over 3 min). H NMR (400 MHz, CDCh) 5 ppm 1.46 (d, ..02 Hz, 9 H) 2.16-2.30 (m, 2 H) 3.55-3.74 (m, 4 H) 5.07 (br s, 1H) 6.67-6.70 (m, 1 H) 6.75 (d, J.02 Hz, 1 H) 6.77 (br s, 1 H) 7.13 (br s, 1 H) 7.28-7.35 (m, 1 H) 7.46-7.48 (m, 2 H) 7.75-7.79 (m, I H) 8.19-8.22 (m, 1 H). MS (ESI+) for C23H2SC1N2O5S2 m/z 526.2 (M+NH4)* 453.0 (M-fBuf, 409.2 (M-Boc)"". HPLC 99%, Rt=2.767 min (System Al, 10-97% MeCN over 3 min). INTERMEDIATE 33 iert-Bntyl 4-[(4-nitro-l-naplithyl)oxy]pipeR1dme-l-carboxylate (General method C) The compound was prepared &om 4-iiilro-l-naplitbol (2 g, 10.6 mmol). The mateR1al obtained after flash C1uomatography was not pure according to NMR. Recrystallization from EtOAcAio-liexane gave 2.3g (62%) of fiie title compoimd as a yellow solid. HPLC 98%, RT=2.842 min (System Al, 10-97% MeCN over 3 min H NMR (400 MHz, CDC13) 5 ppm 1.48 (s, 9 H) 1.99 (m, 4 H) 3.54 (m, 2 H) 3.70 (m, 2 H) 4.87 (m, 1H) 6.82 (d, ..04 Hz, 1H) 7.59 (m, 1 H) 7.74 (in, 1 H) 8.38 (d, 8.53 Hz, 2 H) 8.77 (d, 7=8.53 Hz, I H). MS (ESI+) for C20H24N2OS mh 373.0 (M+H)*, 390.2 (M+MLif, 317.0 (M-iBuf. HPLC 9S%, R1=2.973 min (SystemBl, 10-90% MeCN over 3 min). INTERMEDIATE 34 /cH-Butyl 4-[(4-ainino-l-naphthyl)oKy]pipeR1dm&-l-carboxylate (General Method C) The compound was prepared fiom intermediate 6 (2.3 g, 7.0 mmol). Yield: 2g (95%) as pink oil. HPLC 94%, RT=2.885 min (System BI, 10-90% MeCN over 3 min). H NMR (400MHz, CDCU) 5ppm 1.46 (s, 9H) 1.80-1.98 (m,4H) 3.35-3.41 (m,2 H) 3.46 (s, 3 H) 3.69-3.75 (m, 2 H) 3.88 (br s, 1 H) 4.50-4.54 (m, 1 H) 7.45-7.50 (m, 2 H) 7.79-7.81 (m, 1 H) 8.22-8.24 (m, 1 H). MS (ESI+) for C20H25N2O3 m/z 343.2 (M+H)*. HPLC 94%, R1=2.735 min (System Al, 10-97% MeCN over 3 min). (d„.53 Hz, IH) 6.S3-6.79 (m, 2 H) 7.17 (d, J=S.03 Hz, 1H) 7.39-7M (m, 2 H) 7.61-7.64 (m, 2 H) 7.75-7.77 (m, 1H) 8J21-8.24 (m, 1 H). MS (ESI+) for C27H32N2O6S in/z 530.2 (M+NH4f, 457.2 (M-(B«)"*, 413,4 (M-Bocf. HPLC 99%, RT=2.668 min (System Bl, 10-90%MeCNover 3 mm). INTERMEDIATES? tert-Butyl4-((4-{[(5-flaoro-2-methyIphenyI)solfoiiyI]aiiiiBo}-l-naphthyOoKylpipeR1dine-l-carboxylate (Gensral method E) The conq)oimd was prepared from tert-butyl 4-[(4~amiiio-l-nhthyl)oxy]pipeR1diiie-l-carboxylate (0.25 g, 0.73 nunol). Yield: 0.24 g (64 %) of flie title compound as a pink solid. HPLC 99 %,RT=2.809iiim(SystemBI, 10-90% MeCN over 3 min). HNMR(400 MHz, CDC13) 5ppm 1.46 (s, 9H) 1.83-1.98 (m, 4H) 2.54 (s, 3 H) 3.42-3.48 (m, 2H) 3.63-3.69 (m, 2 H) 4.64-4.68 (m, 1 H) 6.64-6.68 (m, 2 H) 7.03 (d, J=8.53 Hz, 1 H) 7.10 (m, 1 H) 7.22 (dd, J=8.53, 5.02 Hz, 1 H) 7.44-7.48 (m, 2 H) 7.55 (dd, J=S.S3, 2.51 Hz, 1 H) 7,83-7.86 (m, 1 H) 8.24 (m, 1 H). MS (EStf) for C1iHjiFNjOsS m/z 532.2 (M+NH), 459.2 (M-tBu)"", 415.2 (M-Boc). HPLC 100 %, RT=2.877 min (System Al, 10-97% MeCN over 3 min). INTERMEDIATE 39 tert~Bul (iRy3-liydrfaypyrR16ioe-l-carbixsyiate fGen&-al method G) The cony)ottnd was prared &om (3R)-3-hydroxypyrroIidme (5 g, 57.4 nuaol). Yield: 9.6 g (90 %) of fee title compound H NMR (400 MHz, CDCla) 5 ppm 1.43 (B, 9 H) 1.90-1.98 (m, 2 H) 3.27-3.47 (m, 4H) 4.40 (br s, IH). INTERMEDIATE 40 (ert-Butyl (3S)-3-hyclrosypyrrolidine-l-carboxylate (General method G) The compound was prepared from (3S)-3-]jydrox}jTro!idiae (5 g, 51.4 tmaol). Yield; 8 g (86 %) of the title compound. H NMR (400 MHz, CDC13) 5ppm 1.40 (s, 9 H) 1.86-1.91 (m, 2 H) 3.24-3.42 (m, 4H) 4.36 (br s, IH). INTERMEDIATE 41 tert-Butyl (3S)-3-t(4-iiitro-l-Daphthyl)oxy]pyrroIidine-l-carboxylate (General method C) The compound was prepared from terr-butyl (3R)-3-hydroxyp5TroIidiae-3-cart)oxyJa£e (3,56 g, 19 mmol) and 4-mtro-l-nhfliol (3 g, 15.9 mmol). Yield: 5 g (88 %) of the title compound as yellow oil. H NMR (400 MHz, CDC13) 5 ppm 1.45 (d, J=7.03 Hz, 9 EO 2.22-2.38 (m, 2 H) 3.54-3.83 (in, 4 H) 5,18 (br s, 1H) 6.74 (d, J=8,53 Hz, 1 H) 7.56 (t, J=7.78 Hz, 1 H) 7.71 (t, J=7.78 Hz, 1 H) 8.29 (d, J=8.53 Hz, 1 H) S.33 (d, J=8.53 Hz, 1 H) 8.72 (d, J=8.53 Hz, 1 H). MS (ESI+) for C1gHzaNaOs m/z 376.2 (M+NH4)*, 303.2 (M- tBu)*. HPLC 100 %, R-i=2.768 min (System Al, 10-97% MeCN over 3 min). INTERMEDIATE 42 /£rt-BDtyI(3R)-3-((4-jutro-3-Baphfliy])oxy]pyn-olidine-l-carboxylatefGe»eR17/»i£/fiod C) The compound was prepared from ten -butyl (3S)-3-hydroxypyrrolidine-l-carboxylate (3,56 g, 19 mmol) and 4-mtro-l-napli1iiol (3 g, 15.9 mmol). Yield: 2.8 g (49 %) of fee title compound as yellow oil. H KMR (400 MHz, CDC13) S ppm 1.46 (d, J=7.03 Hz, 9 H) 2.26-2.38 (m, 2 H) 3.55-3.81 (m, 4 H) 5.20 (br s, 1 H) 6.77 (d, J=8.53 Hz, 1 H) 7.59 (t. J=7.53 Hz, 1 H) 1.11-1.16 (m, 1 H) 8.32 (d, J=8.03 Hz, 1 H) 8.37 (d, J=S.53 Hz, 1 H) 8.76 (d, J=8.53 Hz, 1 H). HPLC 95 %, RT=2.775 min (System Al, 10-97 % MeCN over 3 min). INTERMEDIATE 43 tert-Buty! (3S)-3-[(4-ammo-l-naplithyI)oxy]pyrrolidine-l-carboiy!ate (General method The compound was prepared from ten -butyl (3S)-3-[(4-nitro-l-n£5ihthyl)oxy]pyrrolidme-1-carboxyIate (5 g, 14 mmol). Yield: 3.5 g (76 %) of the title compound as dark pink solid. HmiR (400 MHz, CDC13) 5 ppm 1.46 (d, J=14.56 Hz, 9 H) 2.08-2.13 (m, 1 H) 2.27-2.30 (m, J=13.05 Hz, 1H) 3.54-3.77 (m, 4 H) 3.88 (br s, 2 H) 4.96 (br s, 1 H) 6.65-6.70 (m, 2 H) 7.45-7.51 (m, 2 H) 7.79-7.81 (m, I H) 8,15-8.19 (m, IH). MS (ESI+) for C19H24N2OJ m/z 329.2 (M+H), 273.2 (M-tBuf, 229.2 (M-Bocf. HPLC 95 %, RT=1.854 min (System Al, 10-97 % MeCN over 3 min). INTERMEDIATE 44 ttrt-Butyl (3R)-3-[(4-amiBO-l-Baphthyr)oxylpyrrolidme-l-carboxyIate (General method D) The coiiq)Oimd was prepared from ten -butyl (3R)-3-[(4-ratro-l-naphthyl)oxy]pyiroIidiae- l-caiboxy!ate (2.8 g, 7.S mmol). Yield: 1-8 g (72 %) of the title compound as dark pink solid. HNMR (400 MHz, CDC13) 5 ppm 1.46 (d, J=14.56 Hz, 9 H) 2.07-2.14 (m, 1 H) 2.27-2.30 (m, 1 H) 3.54-3.77 (m, 4 H) 3.93 (br s, 2 H) 4.96 (br s, 1 H) 6.65-6.70 (m, 2 H) 7.45-7.51 (m, 2 H) 7.79-7.81 (m, 1 H) 8.16-8.18 (m, IH). MS (ESI+) for C19H24N2O3 m/z 329.2 (M+H)"", 273.2 (M-tBu), 229.2 (M-Boc)*. HPLC 94 %, RT=1.751 min (System Al, 10-97% MeCN over 3 min). INTERMEDIATE 45 teM-Butyl(3S)-3-[(4-{[(4-cbloropheiiyl)sulfonyI]amino}-l-naphthyI)oxy]pyrrolidine-l- carboxylate (General method E) The compound was prepared from rert-butyl (3S)-3-[C4-mtro-l-nhthy!)oxy]pyrroIidine- 1-carboxylate (0.3 g, 0.9 mmol) and 4-chloro-phen1siilfonylchloiide (0.23 g, 1.1 mmol). Yield: 0,23 g (50 %) of the title compound. H NMR (400 MHz, CDC13) 5 ppm 1.46 (d, J.52 Hz, 9 H) 2.15-2-34 (m, 2 H) 3.54-3.74 (m, 4 H) 5.05 (br s, 1 H) 6.62-6.71 (m, 2 H) 7.17-7.23 (m, 1H) 7.33 (d, J=8.53 Hz, 1 H) 7.39-7.43 (m, 2 H) 7.62-7.64 (m, 2 H) 7.65-7.70 (m, J=6.02 Hz, 1 H) 8.18 (d, J=8.53 Hz, 1 H) MS (ESH-) for C25H27C1N2O5S m/z 520.2 (M+NH*) 447.0 (M-tBu). HPLC 100 %, RT=2.772 min (System Al, 10-97 % MeCN over 3 min), INTERMEDIATE 46 2£ff-ButyI(3R3-[{4-{[(4-chloropbeoyOsulfonyl]ainuio}-l-naphthyI)oxy]pyrro1!dme-l-carboxylate (General method E) The compound was prqiared fiom lert-butyl (3R)-3-[(4-nitro-l-naplithyl)oxy]pyrrolidine-I-carboxylate (0.3 g, 0.9 mmol) and 4-cfaloro-phCTylsulfanylchloiide (0.23 g, 1.1 mmol). Yield: 0.4 g (S7 %) of the title compound. HNMR(400 MHz, CDC13) 5 ppm 1.46 (d, J=4.52 Hz, 9 H) 2.15-2-34 (m, 2 H) 3.54-3.74 (m, 4 H) 5.05 (br s, 1 H) 6.60-6.66 (m, 2 H) 7.17-7.23 (m, 1 H) 7.33 (d, J=8.53 Hz, 1 H) 7.39-7.43 (m, 2 H) 7.62-7.64 (m, 2 H) 7.65-7.70 (m, J=6.02 Hz, I H) 8.18 (d, J=8.53 Hz, 1 H) MS (ESI+) for C25H27C1N205S m/z 520.2 (M+NHsf, 447.0 (M-ffiu)"". HPLC 100 %, RT=2.769 min (System Al, 10-97 % MeCN over 3 rain). EXAMPLE 32 4-ChIoro-N-|4-(pyrrolidm-3-yloxy)-l-naphthyI]beiizenesiilf(raamide hydrochloR1de (General method F) The compound was prepared from intCTmediate 3 (0.13 g, 0.26 mmol). The solid was further puR1fied by tR1turation wifli diethyl ether giving 0.1 Ig (95%) of the title compound as white solid. HPLC 98%, RT=1.810 min (System Al, 10-97% MeCN over 3 min). H NMR (400 MHz, DMSO-de) 6 ppm 2.21-2.26 (m, 2 H) 3.32-3.37 (m, 2 H) 3.48-3.50 (m, 2 H) 5.28 (br s, 1 H) 6.91-6.98 (m, 2 H) 7.44-7.50 (m, 2 H) 7.56-7.64 (m, 4 H) 7.88-7.90 (m, 1 H) 8.20-8.23 (m, 1 H). MS (ESI+) for CzoH,9ClN203S m/z 401.2 (M+H). HPLC 98%, RT=1.651 mJn(SBteinEl, 10-90% MeCN over 3 min). EXAMPLE 33 4-MetJioxy-N-[4-(pyrroUdinO-yloxyl-naph(liyI|beiizettesBlfonaiiiide hydrochloR1de (General method F) Hie compound was prepared from intermediate 4 (0.18 g, 0.36 mmol), yield: 0.12 g (76%) of the title compoimd as a white solid. HPLC 100%, RT=I.490 mjn (System Bl, 10-90% MeCN over 3 min). HNMR (400 MHz, DMSO-ds) 5 ppm 2.20-2.25 (m, 2 H) 3.31-3.53 (m, 4 H) 3.7S (s, 3 H) 5.27 (br s, 1 H) 6.90-6.97 (m, 2 H) 7.00 (d, /=8.53 Hz, 2 H) 7.43-7.48 (m, 2 H) 7.57 (d, 8.53 Hz, 2 H) 7,93-7.96 (m, I H) 8.19-8.22 (m, 1 H) 9.63 (br s, 2 H). MS (ESH-) for C21H23N2O4S m/z 409.2 (M+H)*. HPLC 100%, RT=1.639 min (System Al, 10-97% MK:ir over 3 min). EXAMPLE 34 5-ChIoro-N-[4-(pyrrolidin-3-j1oxy)-l-ttaphthyI]thiophene-2-sQUonaniide hydrochloR1de (General method F) The compound was prepared &om intCTmediate 5 (0.20 g, 0.39 mmol). Yield: 0.14 g (80%) of the title compound as apale white solid. HPLC 99%, RT=1.65I min (Stem El, 10-90% MeCN over 3 min). H NMR (400 MHz, DMSO-de) 5 ppm 2.23-2.26 (ra, 2 H) 3.28-3.39 (m,2H) 3.40-3.56 (m,2H) 5.32(br s, 1H) 6.99 (d, J=8.53 Hz, 1 H) 7.13 (d,/=S.Q3 Hz, 1 H) 7.15 (d, /.02 Hz, 1 H) 7.26 (d, 4.02 Hz, 1 H) 7.48-7.52 (m, 2 H) 7.92 (dd, 6.53,3,01 Hz, 1 H) 8,25 (dd, /-6.53,3.01 Hz, 1 H) 9.60 (s, 1 H). MS (ESI+) for C1SHITONZOSSZ m/z 409,2 (M+H)*. HPLC 99%, RT=1 .818 min (System Al, 10-97% MeCN over 3 min). EXAMPLE 35 4-Chloro-N-{4-(pipeR1diD-3-yloxy)-l-napbyl]l)ei]zeaesuUoQa]mde hydrochloR1de (General method F) The compound was prepared fiom intermediate 8 (0.26 g, 0.50 mmolX Yield: 0.12 g (53%) of the title compound as a white solid. HPLC 100%, R-i=1.872 min (System Al, 10-97% MeCN over 3 min).H mst (400 MHz, DMSO-de) 5 ppm 1.95-1.99 (m, 2 H) 2.14-2.19 (ra, 2 H) 3.11 (br s, 2 H) 3.26 (br s, 2 H) 4,84 (br s, 1 H) 6.92-6.99 (m, 2 H) 7.44-7.51 (m, 2 H) 7.57-7,65 (m, 4 H) 7.91 (d, 7.53 Hz, 1 H) 8.17 (d, Mim Hz, 1 H) 8.94 (br s, 1 H) 9.05 Cbr s, 1 H) 10.11 (s, 1 H). MS (ESI+) for C2iH2iC!N203S m!z 415.2 (M+H)*. HPIX 99%, RT=1.6S7 min (Sjm Bl, 10-90% MeCN over 3 min). EXAMPLE 36 4-Metho-N-I4-(pipeR1diB-3-ylo)-l-naphaiyl]beiizeDesiilfoHamide hydrochloR1de (General method F) The compound was prepared fiom intermediate 9 (0.19 g, 037 mmol). Yield: 0.15 g (90%) of the title compound as a white solid. HPLC 97%, RT=1.508 min (System Bl, 10-90% MeCN over 3 min). HNMR (400 MHz, DMSO-ds) 5 ppm 1.96 (m, 2 H) 2.16 (m, 2 H) 3.10 (m, 2 H) 3.26 (m, /=6.02 Hx, 2 H) 3.78 (s, 3 H) 4.82 (m, 1H) 6.95 (q,..20 Hz, 1 H) 7.01 (d, =9.04 Hz, 2 H) 7.47 (m, 2 H) 7.57 (m, 2 H) 7.96 (m, 1 H) 8.16 (m, 1 H) 8.96 (s, 1H) 9.07 (s, 1 H) 9.81 (s, 1 H). MS (ESI+) for C22HMN2O4S ni/z 413.4 (M+H)"". HPLC 97%, RT=1.713 min (System Al. 10-97%MeCN over 3 min). EXAMPLE 37 5-Fiuoro-2-methyI-N-[4-(pipeR1dm-4-yIoxy)-l-napIithyI]beDzenesnIfonaimde hydrochloR1de (General method F) The compound was prepared fiom intermediale 10 (0.24 g, 0.47 mmol). Yield: 0.21 g (9 9 %) of tiie title coniound as an off-white soHd. HPLC 100 %, RT=1.823 min (System Al, 10-97 % MeCN over 3 min). H NMR (400 IVtHz, CHsOH-d,) S ppm 2.13 (m, 4 H) 2.42 (s, 3 H) 3.18 (m, 2 H) 3.37 (m, 2 H) 4.83 (m, 1H) 6.81 (d, 8.53 Hz, 1 H) 6.97 (d, /=8.03 Hz, I H) 7.10 (m, 1H) 7.24 (m, .8.53, 5.52 Hz, 1 H) 7.35 (m, 3 H) 7.83 (m, 1 H). MS (ESI+) for C1HzjFNiOsS W2415.2 (M+H)"".HPLC 96 %, R1=1.628 min (System Bl, 10-90% MeCN over 3 min). EXAMPLE 38 5-Ch!orft-N-[4-(pipeR1dui-4-yIoxy)-l-naphthyl]thiophene-2-salfonainide hydrochloR1de (General method F) The compound was prepared from tert-butyl 4-[(4-{[(5-fluoro-2 methylpheny!)- sulfonyl]aniino}-l-nhthyl)oxy]pipeR1dine-l-carboxylate (0.24 g, 0.46 mmol). Yield: 0.16 g (76 %) of the title conjomd as a white solid. H NMR (400 MHz, DMSO-de) 5 ppm 1.96-2.03 (m, 2 H) 2.16-2.22 (m, 2 H) 3.09-3.14 (m, 2 H) 3.25-3.31 (m, 2 H) 4.86-4.89 (m. 1 H) 7.04-7.11 (m, 2 H) 7.16 (d, 4.02 Hz, 1 H) 7.26 (d, 4.02 Hz, 1H) 7.48-7.53 (m, 2 H) 7.92-7.94 (m, 1 H) 8.19-8.21 (m, 1 H) 9.06 {br s, 1 H) 10.36 (br s, 1 H). MS (ESI+) for C1sHieClNiOjSa m/z 423.0 (M+H)"". HFLC 99 %, RT=1.861 mm (System ii.1,10-97 % MeCN over 3 min). Legend to Scheme 5: i) Malonic aC1d, pjFR1dine, pipeR1dine, heat; ii) ethylchlorofiiniiate, acetone, Ns -]0 °C; iii) diphenyl ether, 220 "C; iv) POCh, heat; v) gas SOj, n-EuLi, N-chlorosuccminR1de, CHiQj; vi) R-NH2, pjR1dine; vii) HR, KJCOJ, DMSO, heat. INTERMEDIATE 47 (2£)-3-(S-Bromothieii-2-yl) acrylic aC1d Malonic aC1d (44.40 g, 426.7 mmol) was added to a mixture of 5-bromothiophMie-2-carbaldehyde (50 g, 261.7 mmol), pipeR1dine (2.84 mL) and pyR1dine (150 mL). The roixture was reflnxed for 1 h at 80°C and than at 100 "C over night The volatiles were evorated and the rdue was dissolved in water and aC1dified with hydrochloR1c aC1d (pH 2). The crude product was crystallized in ethanol. Yield: 55.24 g (90.5 %). H MMR (270 MHz, CH30H-d4) 5 ppm 6.14 (d, 15.83 Hz, 1 H) 7.11-7.16 (m, 2 H) 7.6S (d, /=16.36 Hz, 1 H); MS 233.1 (M - H)*; PuR1ty (HPLQ 94 %. INTERMEDIATE 48 (2E)-3-(5-BromotMen-2-yI) acryloyl azide Thionyl diloR1de (1.04 mL) was added to a solution of (2£)-3-(5-bromothien-2-yl) acrylic aC1d (1.04 g, 4.46 mmol) in chloroform (20 mL) and the mixture was refluxed for 2h at 75°C and than used in the next step. The above solution was added drop wise to a stirred suspension ofsodium azide (0.58 g, 8.93nmiol), dioxaDe(3niL)andwatw(3 mL)inan ice bath. After 10 min a preC1pitate speared which was filtered off and washed with water. The residue was dissolved in dicbloromethane, dR1ed with MgS04, filtered and the solvent was removed to afford: 0.96 g (83.4 %). H NMR (270 MHz CHOH-dA) 5 ppm 6.20 (d, 15.57 Hz, ] H) 7.15-7.25 (m, 2 H) 7.80 (d, 15.57 Hz, 1H); MS 258.1 (M - H)*; PuR1ty (HPLC) 65%. INTERMEDIATE 49 2-BroniDfliieDO I3,2-r] pjTidin-4 (5B)-oiie A solution of (2F)-3-(5-bromothien-2-yl) acryloyl azide (18.00 g, 69.7 mraol) solved in dichloromethane (100 mL) was added dropwise to diphmiyl ether (90 mL) at 150 "C. The temperature w increased to 220°C for Ih. The mixture was cooled to room temperature followed by the addition of ether. Tlie solid preC1pitated and was separated by filtration. Yield: 13.58 g (84.6 %), H NMR (270 MHz, DMSO-ds) 5 ppm 6.82 (d, J=l.n Hz, 1 H) 7.27 (d, 6.86 Hz, 1 H) 7.54 (s, 1 H) 11.55 (s, 1 H); MS 230.1 (M- H)*; PuR1ty (HPLC) 92 %. INTERMEDIATE 50 2-Bromo-4-C1i!oro-tliieno [3;2-c] pyR1dioe Phosphorus oxychloR1de (4.08 g, 26.6 mmol) was added dropwise to 2-bromothieno [3,2-c] pyR1din-4 {5-one (2.04 g, 8.87 mmol) at 0 "C. The mixture was heated at 135 =C for 2.5h, then care&lly poured over ice water. The precq)itated was collected by filtration and dR1ed to yield 1.78 g (80.7 %) of title product. H NMR (270 MHz, CHsOH-di) S ppm 7.67 (d, 1H) 7.88 (dddd,6.33 Hz, 2 H) 8.19 (d,/=5.54Hz, 1 H);MS 248.0 (M-H)*; PuR1ty (HPLC) 100 %. INTERMEDIATE 51 and INTERMEDIATE 52 4-ChlorotIiieiio [3,2-c] pyR1(iine-2-snlfoa;4 chloR1de and 2-bronio-4-cMorothieiio [3,2- c] pyR1diiie-3-sulfonyl chloR1de n-Butyi lithium (1,5 mL, 2.4 mmol) was added to 2-bromo-4-cMorotMeno [3,2-c] pyR1dine (0.5 g, 2 mmol) dissolved in dry THE (15 ml) at-78°C under nitrogen. The mixture was stirred for 40 min. The above solution was added to a dry efher saturated wifli SO2 (gas) at -78°C. The mixture was wanned to room temperature, followed by the addition of ether. The preC1pitate was separated by filtration. The two title products were obtained and taken to the next step without further puR1fication as follows: N-chlorosucC1nimide (2.07 g, 10.3 mmol) was added to [(4-chlorothieno [3,2-c] pyR1diQ-2-jl) sulfonyl] hthlum and [(2-bromo-4-chlorolhieno [3,2-c] pyiidin-3-yl) sulfonyl] lithium in dichloromethane (150 mL) at 0 °C. Tlie mixture was heated at 60 *C for 2h, extracted with water (3 x SO mL). The organic phase was separated, dR1ed with MgS04, filtrated and the volatiles were eliminated by vacuum distillation. The crude products were used in the next step without fiather puR1fication. INTERMEDIATE 53 and INTERMEDIATE 54 4-CbIor»-2-thieao [3,2-c] pyR1dine-2- sulfonic aC1d p-toly!amide and 2-bromo-4- ehloro-thieBo[3,2-c]pyR1dine-3-suIfoiiic aC1d p-tolylamlde p-Toludine (30 mg, 2.87 mmol) was added to a solution of 4-ohlorothieno [3,2-c] pyR1dme-2-sulfonyl chloR1de and 2-bromo-4-chlorotMeR1o [3,2-c] pyR1duie-3-sulfonyI chloR1de (0.07 g, 0.26 mmol) in (Kchloromsthane and pyR1dine (0.19 mL). The reaction was stirred at room temperature for 2IL The solvent was ranoved and the crude mixture was taken to the next step wifliout further purtficatiorL EXAMPLE 41 and EXAMPLE 42 4-(4-Metbyl-piperazm-l-yO-tliieiio[3,2-c]pyR1diae-2-siiIfonic aC1d p-totylamide hydrochloR1de and 2-bromo-4-(4-methyl-piperazm-l-yI)-thieno[3,2-clpyR1dhie-3-sulfonic aC1d p-tolylamlde hydrochloR1de A mixture of 4-chloro-2-thiaio [3,2-c] pyR1dine-2- sulfonic aC1d p-tolylamide and 2-bromo-4-ch]oto-thieno[3,2-c]pyR1dine-3-sulfonic aC1d p-tolylamide (70 mg, 0.21 mmol) in DMSO (2 mL), 1-methyl piperazme (0.344 mL, 3.1 mmol) and K2CO3 (28.5 mg, 0.21 mmol) was heated to 1OCC over night. The reaction mixture was dissolved in wata- and extracted with ethyl acetate (3x10 mL). The organic layers were collected and the solvent was removed. The products were puR1fied by HPLC to afford 1.9 mg of 4-(4-Mefliyl-piperazin-l-yl)-tliieno[3,2-c]pyR1dine-2-sulfonic aC1d p-tolylamide. The free base was converted into the hydrochloR1de salt by treatment wifli HC1 in ethen H NMR (270 MEIz, Methanol-d4) S ppm 2.26 (s, 3H) 2.98 (s, 3 H) 3.40-3.55 (m, 8 H) 7.02-7.10 (m, 6 H) 7.55 (d, 5.81 Hz, 1 H) 7.69 (s, 1 H) 8.13 (d, 5.81 Hz, 1 H); LC-MS 403 (M + H)*; PuR1ty (LC-MS) 92 % and 3.8 mg 2-bromo-4-(4-mefliyI-piperazin-l-y!)-thieno[3,2-c]pyR1dine-3-sulfonic aC1d p-tolylaraide. The free base was converted into flie hydrochloR1de salt by treatment with HC1 in eflier: H NMR (270 MHz, Methanol-d4) 5 ppm 2.21 (s, IH) 3.00 (d, 3H) 3.50-3.77 (m, 8 H) 7.00-7.10 (m, 6 H) 7.63 (d, =S.81 Hz, 1 H) 8.19 (d, 5.81 Hz, 1 H); LC-MS 481 (M -1- H)*; PuR1ty (LC-MS) 98 %. Reaction of sulf onyl chloR1de with amin (Method H) To a solution ofthe amine (1.3 equiv.) and pyR1dine (S equiv.) in DCM was added ttie sulfonyl chloR1de (1 equiv.) and tiie reaction mixture was stirred over nit. Aiter addition of TR1samine"" (ca 2 equiv.), the mixture was gently shaken for additional 3 h. The suspension was then filtered through a short silica plug by the aid of DCM and ethyl acetate. The solvent was evaporated, and the residue was dissolved in DCM and washed with 1 M aqueous HC1 (2 times). The combined organic phases were dR1ed (MgS04), filtered, and the solvent was removed to give the sulfonamide product. In cases of low- puR1ty mateR1al, fte products were puR1fied by silica gel flash chromatography. The products are used m die next step (Procedure B). Coupling with aromatic amiDes (Method I) To the reaction mixttires fi»m the Mefliod H, dissolved in DMSO (2mL), amines (15 equiv.) and K2CO3 (1 equiv.) are added. The reactions are stirred at 100°Cfor24andfiian concentrated. The products are puR1fied by LC-MS. The solvents are renaoved under vacuum by SpeedVac and puR1fied by preparative LC/MS. The products that we not pure enough (PuR1ty 0%) wwe puR1fied by preparative chromatography using acetonitR1le-water gradients containing 0.1% tR1flouroacetic aC1d. After HPLC analysis fiactions ihai were 90% pure were collected and concentrated. Deprotection of the amine in die piperazine was performed by first dissolving the substance in meftianol and adig portions of IM HCVether. The reactions are analyzed by TLC- The solvents were concentrated under vacuum by a SpeedVac, Deprotection of BOC-groop (Method L) The sulfone or sulfonamide dsivative (prepared by Methods H and I) were dissolved in a small amount of MeOH/DCM 1:1 and treated with an excess of 1 MHC1 in diethyl ether. StirR1ng at ambient tenerature ovemi resulted in a preC1pitate which were collected by filtration to give the products as their corresponding hydrochloR1de salts. EXAMPLE 43 4-(4-MethyJpiperazni-l-yl)-N-phenylthieno[3,2-c]pyR1diiie-2-SDlfonaniide hydrochloR1de The synthesis was preformed essentially as descR1bed in Method H-L. Yield: 8.1 mg (33.8 %). H fMR (270 MHz, CHjOH-d,) 5 ppm 8.13 (d, /=5.81 Hz, I H) 7.67 (s, 1 H) 7.54 (d, J=5.81 Hz, 1 H) 7.55-7.53 (m, 5H) 2.97 (s, 3 H) {4H obscured by solvent signal); LC-MS 389 (M - Kf; PuR1ty (HPLC) 100 %. EXAMPLE 44 4-PiperaziB-l-yI-(Jiieiio[3c]pyR1dine-2-snlfonicaC1d(3-fluoro-5-fR1flaoromethyI-pheayl)-amide hydrochloR1de l~[2 EXAMPLE 45 4-Piperazin-l-yI-thienol3-c]pyR1dine-2-STUfonic aC1d (4MdiloR1-phenyI)-aiiiide hydrochloR1de 4-Chloro-thieno[3,2-c]pyR1dine-2-sulfonic aC1d (3-fluoro-5-tR1fIuorometliyl-phenyl)-aimde (0.208 mmol, 1 equiv.) was used as the tfaienopyR1dine in Meftiod H-L. Yield: 7.2 mg HPLC: tR= 3.039 (System: 5 % to 50 % ACN in 3 min, CS), PuR1ty: 100%, LOMS: tR= 0.905 (System: 30 % to 60 % ACN in 1.5 min, Hypersil BDS), PuR1ty: 97%. MS: 409 (M+1). H NMR (270 MHz, CHsOH-dj) 5 ppm 3.50 (m, 4 H) 3.91 (m, 4 H) 7.25 (m, 4 H) 7.71 (dd, 6.33, 0.53 Hz, 1 H) 7.96 (d,0.79 Hz, 1H) 8.04 (d, /=6.33 Hz, 1 H). EXAMPLE 46 4-Pipei-aziQ-I-yl-thieno[3]pyR1cluie-2-sulfonic aC1d (4-isopropy!-pheny0-aniide bydrochloR1de 4-ChIoro-thieno[3,2-c]pyR1dine-2-sulfonic aC1d (4-isopropyI-phenyI)-ainide (0.201 nimol, I equiv.) was used as the thienopyR1dine in Method H-L. Yield: 6,9 mg HPLC: tR= 3.255 (System: 5 % to 50 % ACN in 3 min, 08), PuR1ty: 95%, LC/MS: tR= 1.255 (Sjtem: 30% to 60 % ACN in 1.5 min, Hypersil BDS), PuR1ty: 98 %. MS: 417 (M+1). H NMR (270 MHz, CH30H-d4) 5 ppm 1.18 (d, =6.86 Hz, 6 H) 2.83 (m, 2 H) 3.52 (m, 4 H) 4.00 (m, 4 H) 7.14 (m, 3 H) 7.75 (d, J=6.60 Hz, 1 H) S.02 (m, I H). EXAMPLE 47 4-Piperazin-l-yI-thieno[3,2-c]pyR1dine-2-stilfoDic addp-tolylamide hydrochloR1de To a solution of 4-chloro-thieno[3,2-c]pyR1dine-2-sulfonyl chloR1de (0.640 g, 2.39 mmol) in DCM (20 mL) was added pyR1dine (1.9 mL, 23.9 mmol) followed by p-tolylamine (0.307 g, 2,86 mmol). The reaction mixture was stirred at room temperature for 16 hoius. The mixture was concentrated aiwi re-dissolved in DMSO (10 mL), piperazine-I-carboxylic aC1d iert-butyl ester (1.34 g, 7.17 mraol) ajidK2C03 (0.989 g, 7.17 nunol) were added. The mixture was stirred at 100 °C for 16 hours and then conceniiated. The crude reaction mixture was dissolved in EtOAc (100 mL) and washed with bR1ne (2 x 50 mL). The organic phase was dR1ed (NajSO) and concentrated. The crude intermediate was puR1Sed by column chromatography on silica using EtOAc/?J-pentane (1:1) as eluent. The intermediate was dissolved in EtOAc/MeOH and dieiiiyl ethra- saturated with HCl (g) was added. The mixture was stirred at room toterature for 16 hours. The preC1pitate was collected by filtration and washed with diethyl ether/n-pentane to give 0.475 g of the crude product. PuR1fication by preparative reversed phase HPLC gave 0.133 g of the pure product: H NMR (DMSO-de, 25 "C, 270.17 MHz) 5 10.61 (br s, IH), 9.23 (br s, 2H), 8.13 (d, J = 5.80 Hz, IH), 7.91 (s, IH); 7.67 (d, J = 5.80 Hz, IH), 7.09-7.07 (m, 4H), 3.68-3.59 (m, 4H), 3.33-3.22 (m, 4H), 2.20 (s, 3H); m/z (posESI) 399 (M+H). EXAMPLE 48 4-{4-MethyIpiperazin-l-yI)-A- C2-cyC1ohex-l-eD-l-yleflij1) fiiieno [ic] pyR1dJne-2- sulfonamide hydrochloR1de The synthesis was preformed essentially as descR1bed in Mefeod H-L. Yield: 25.6 mg H NMR (270 MHz, DMSO-de) 5 ppm 10.49-10.48 (m, IH) 8.23-7.95 (m, 3H) 7.72-7.71 (m, IH) 5.34-5.33 (m, IH) 4.14-4.11 (m, 2H) 3.53-3.51 (m, 2H) 3.29-3.25 (m, 2H) 2.9S-2.97 (m, 2H) 2.85 (s, 3H) 2.04-1.81 (m, 4H) 1.57-1.15 (m, 8H); LC-MS 420.17 (M - H)*; PuR1ty (LC-MS) 97 %. EXAMPLE 49 2-((4-MeaiyIpiperazm-l-yl) thieno [3-c] pyR1din-2-ylsiilfonyI)-l,2,4- tetrahydrolsoqniaoline hydrochloR1de The synthesis was preformed essentially as descR1bed in Mefeod H-L. Yield: 15.5 mg H NMR (270 MHz, DMSO-dg) 5 ppm 10.49-10.48 (m, IH) 8.17-8.15 (m, IH) 7.86-7.85 (m, IH) 7.70-7.65 (m, 2H) 7.28-7.12 (m, 3H) 3.97-3.94 (m, 2H) 3.87-3.85 (m, 2H) 3.25-3.18 (m, 2H) 2.84 (s, 3H) 1.67-1.65 (m, 2H) 3.51-3.34 (6H obscured by solvent signal); LC-MS 428.13 {M - H)*; PuR1ty (LC-MS) 99 %. EXAMPLE 50 4-(4-Methylpipera2m-l-yI)-iV- C2-thieii-2-ylethyl) thJeno [31 pyR1dine-2- solfonainide hydrochloR1de The synthesis was prefonned esseitially as descR1bed in Mettiod H-L. Yield: 29.5 mgH NMR (270MHz,DMSO-de) Sppm 10.28-10.27 (m, IH) 8.34-8.33 (m, IH) S.19-8.17 (m, IH) 8.01-8.00 (m, IH) 7.71-7.69 (m, IH) 7.31-7.30 (m, IH) 6.91-6.87 (m, IH) 4.13-4.10 (m, 2H) 3.53-3.51 (m, 2H) 3.29-3.25 (m, 2H) 3.17-3.16 (m, 2H) 2.99-2.95 (m 4H) 2.86 (s, 3H); LC-MS 422.09 (M - H)*; PuR1ty (LC-MS) 99%. EXAMPLE 51 4-(4-Methylpiperazin-l-yI)-JV- [l-(l-naphthyl) ethyl] thieno [3,2-c] pyrldiae-2- sQlfonamide hydrochloR1de The syii&esis was preformed essentially as descR1bed in Method H-L. 20.1 mg H NMR (270MHz,DMSO-ds) Sppm 10.28-10.27 (m, IH) 8.85-8.84 (m, IH) 8.02-8.01 (m, IH) 7.67-7.60 (m, 4H) 7.53-7.50 (m, 2H) 7.39-7.36 (m, 2H) 4.72-4.70 (m, IH) 3.S7-3.84 (m, IH) 3.72-3.70 (m, IH) 3,23-3.13 (m, 4H) 2.84 (s, 3H) 1.42-1.40 (m 3H); LC-MS 466,15 (M - H)""; PuR1ty (LC-MS) 99 %. EXAMPLE 52 4-(4-Metfaylpiperaziii-l-yl)-iV- (4-herylphenyF) thieno [3,2-c] pyR1diiie-2-suIfonamide hydrochloR1de The synthesis was preformed essentially as descR1bed in Metiiod H-L. 8.0 mg H NMR (270 MHz, DMSO-dft) 5 ppm 10.39-10.38 (m, IH) 8.16-8.15 (m, IH) 7.90-7.89 (m, IH) 7.66-7.65 (m, IH) 7.09-7.08 (m, 4H) 4.00-3.98 (m, 2H) 3.51-3.48 (m, 2H) 3.26-3.22 (m, 2H) 2.85 (s, 3H) 2.49-2.45 (m, 2H) 1.48-1.46 (m, 2H) 1.24-1.22 (m, 8H) 0.82-0.81 (m, 3H); LC-MS 472.20 (M - Ef; PuR1ty (LC-MS) 98 %. EXAMPLE 53 N- (3-Clilorobeiizyl)-4-(4-metltylpiperaziii-l-yI) thieno [3] pyR1dine-2-saIfoaainide hydrochloR1de The synthesis was preformed essentially as descR1bed in Method H-L, 30.7 mg H NMR (270 MHz, DMSO-dfi) 5 ppm 10.25-1024 (m, IH) 8.78-8.77 (m, IH) 8.18-8.17 (m, IH) 7.91-7.90 (m, IH) 7.68-7.67 (m, IH) 7.26-7.19 (m, 3H) 4.21-4,20 (m, 2H) 4.08-4.05 (m, 2H) 3.54-3,51 (m, 2H) 3.28-3-23 (m, 2H) 2.87 (s, 3H) 2.84-2.60 (2H obscured by solvent signal); LC-MS 436.08 (M - H)*; PuR1ty (LC-MS) 94 %. EXAMPLE 54 4-(4-Methylpiperazin-l-yl)-iV- Il-(4-flnorophenyr) efliyl] thieno [3-c] pyR1dme-2- sulfonamide hydrochloR1de The synthesis was prefonaed essentially as dracR1bed inMeOiod H-L. 32,9 mg H 1 EXAMPLE 55 JV- (2-DiIluorobenzyl)-4-(4-methylplperazui-l-yI) thieno [3cl pyR1dine-2- salfooamide hydrochloR1de The synthesis was preformed essentially as dracR1bed in Method H-L. 26.7 mg H NMR (270 MHz, DMSO-dfi) 5 ppm 10.36-10.35 (m, IH) S.82-8.81 (m, IH) 7.96-7.95 (m, IH) 7.69-7.62 (m, IH) 7.27-7.10 {m, 2H) 4.26-4.25 (m, 215) 4.11-4.08 {m, 2H) 3.54-3.52 (m, 2H) 3.28-3-24 (m, 2H) 2.68 (s, 3H) 2.86-2.60 (2H obscured by solvent signal); LC-MS 438.10 (M - H)*; PuR1ty (LC-MS) 93 %. EXAMPLE 56 4-(4-Methytpiperaziii-l-yO-Af- (4-cliloro-2,5-diroethoxyphenyI) thieno [3-c] pyR1dine2-siilfoDainide hydrochloR1de The synfliesis was prefonned essentiaJly as descR1bed in Method H-L. 14.6 mg H NMR (270 MHz. DMSO-dfi) 5 ppm 10.27-10.26 (m, IH) 10.14-10.13 (m, IH) 8.18-8.17 (m, IH) 7.S3-7.82 (m, IH) 7.69-7.68 (m, IH) 7.09-7.07 (m, 2H) 4.00 (s 2H) 3.76-3.75 (ra, 2H) 3.51-3.4S (m, 2H) 3.24-3.22 (m, 2H) 2.85 (s, 3H); LC-MS 482.08 (M- H); PuR1ty (XC-MS) 95 %. IH) 7.80-7.79 (m, IH) 7.26-7.25 (m, IH) 4.55-4.52 (m, IH) 3.54-3.52 (m, 2E) 2.88-2.87 (rn, 3H) 1.3S-1.36 (m, 3H) 3.17-2.83 (6H obscured by solvent signal); LC-MS 512.04 (M -H)+; PuR1ty (LC-MS) 93%. I EXAMPLE 63 4-Kperaan-l-yUN-I-3-(trffliioromfcfeyl)piieflyI]1iiienot34-clpyridiB&-2-sTitfoaanuae hydrochloride Tiie synthesis was preformed essentially ss described in Method H-L. Yield: 2.6 mg (1.2 %). 'H NMR (270 MHz, CH1OH-dj) 5 ppm 8.05 (d, J=6.60 Hz, 2 H) 7.81-7.60 (m, 3H) 7.50-7.47 (m, 2H) 3.94-3.90 (m, 4H) 3.56-3.49 (m, 4H); LC-MS 443 (M - H)""; Purity (HPU:) 99 %. EXAMPLE 64 N-(3-EtbylphenyI)-4-piperaziB-l-yItliienQl3j2-c]pyridiae-2-suIfoiuniidehydrochlQrule The synthesis w piefonoed essaitiaJIy as described ia Mefeod H-L. Yield: 1.4 rag (0.7 %). 'HNMR (270 MHz, CH1OH-A)) 8 ppm 8.35 (s, IH)7.58-6.92 (m, 7H) 3.54-3.44 (m, 2H) 3.01-2.95 (m, 4H) 2,66 (s, IH) 2.18-2.01 (m, 3H)); LC-MS 403 (M - H/; Piirily CHPLC) 100 %. EXAMPLE 65 N-(3,4~DunethoxyphenyI)-4-piperazin-I-yItIiienopc]pyridiiie-2-suIfonamide hydrochloride The synthesis was preformed essentially as described in Method H-L. Yield: 7.7 mg (3.6 %). 'H NMR (270 MHz, CH1OH-d,) 3 ppm 8.04 (d,,=6.60 Hz, 1H) 7.77-7.75 /m, 2H) 6.85-6.83 (m, 2H) 6.68-6.83 (m, IH) 3.87-3.85 (m, 4H) 3.77-3.75 (m, 6H) 3.49-3.45 (m, 4H) 2.65 (s, IH); LC-MS 435 (M - H)""; Pmty (HPLC) 98 %. EXAMPLE 66 N-(4-Bromo-2-mefliylpbenyI}-4-piperariii-I-yltliieiio[3,2-c]pyridiiie-2-sulfoaaniide hydrochloride The synfliesis was prefonned essentially as described in Mefliod H-L. Yield: 12,2 mg (5.3 %). 'H NMR (270 MHz, CH1OH-d,) 5 ppm S.07 (d, 6.33 Hz, 1 H) 7.S6-7.79 (m, 2H) 7.40 (d,1.58 Hz, 1 H)7.30-7,29 (ffl. IH) 7,08 (d,>8.71 Hz, 1 H) 3.96-3.92 (m, 4H) 3.53-3.51 (4H) 2.66 (s, IH) 2.11 (s, 3H); LC-MS 467 (M - H)*; Parity (HPLC) 90 %. EXAMPI£67 2-(4-Piperariii-l-yl-thieBoI5,2-clpyridine-2-SBlfonl3,4-tetra!iydro-isoquinolii»e hydrocbloride The synthesis was piefonned essertially as described in Method H-L fixim 4-[2-(3,4-daKydrQ-tH-isoquinoUne-2-sulfonyi)-thJo[3,2K;]pyridin-4-yl]-pip£aBzine-l-carboxyMc acid lert-butyl ester (0.23S mmol, 1 eqmv.). Yield: 4.0 va$. LC/MS: IB= O.SQl (Syston: 30 % to 60 % ACN in 1.5 min, Hypersil BDS), Purity: 92%. MS: 415 (M+1) IH NMS. (270 MHs,DMSO-ds)5ppm2.87 (t,>=5.81 Hz, 2H) 3.30(s, 4H) 4.43 (s,2R)7.15 (m, 4H) 7.70 (d,/=S.54 Hz, 1 H) 8.12 (s, 1H) 8.18 (d, =5.54 Hz, 1 H) 6 aliphatic protOTia were obecared by the water-peafe in the spectra and so could not be analyzed. EXAMPLE 68 4-PiperaBii-l-yV-thieB6[31pyridiBe-2-sulfonic add (2- hydrochloride The synthesis was piefonned esseatiidly as described in Method H-L &om 4-[2-(2-tMophai-Z-yl-«thylsolfajnoy!)-thieQo[3,2-c]pyridin-4-yl]--pipCTazine-l-Garboxylic acid tert-butylester (0235 mniol, 1 equiv.). Yield; 8.7 mg. LOMS: k= 0.430 (System: 30 % to 60 % ACN in 1.5 min» Hypersil BDS), Purity; 93 %. MS; 409 (M+l) 'H NMR (270 MHz, DMSO-de) 6 ppm 2.25 (s, 1H) 2.75 (s, 1H) 2.96 (t,/=6.99 Hz, 1H) 3.16 (q, ..51 Hz, 1 H) 3.31 (s, 4 H) 3.70 (s, 4 H) 6.90 (m, 1 H) 7.32 (t, >5.54 Hz, 1H) 7.70 (d, 5.S1 Hz, 1 H) 8.04 (d, >1.85 Hz, 1H) 8.15 (d, J5.54 Hz, 1H) 8.36 (m, 1 H) 9.05 (s, 1 H>. EXAMPLE 69 4-Piperaziii-I-ylrthieiiol3,2-clpyridiiie-2-SHtfonic acid (4-cMoro-2,5-dimethosy- p)ienyl)-3niide hydrodiloride The synfliesis was preformed essentially as described in Method H-L from 4-[2-(4-chIoro-2,5-dimelhoxy-phmylsolfemoyl)-tin6no[3,2-;)pyridin-4-yl3-pipeTa2m6-l-carboxy!i rert-butyl ester (0.112 nunoL 1 eqaiv.) was used as the 1hieDC5>yridine in Method C. Yield; 14.7 mg. LC/MS; tR= 0.610 (System; 30 % to 60 % ACN in 1.5 min, YMC), Piaity: 92 %. MS: 469 (M+l)'HKMR(270MHz,DMSO-ds)5ppm3.17 (s, 1 H) 3.27 (s, 4H>3.3S(s, 3 H) 3.58 Cd,.=4.22 Hz, 4 H) 3.77 (s, 3 H) 7.08 (s, I H) 7.69 (d,7=5.81 Hz. I H) 7.81 (s, 1 H) 8.16 (d, =5.81 Hz, 1 H) 9.07(3,1 H) 10.17 (s, 1 H). EXAMPLE 70 4-PiperaziB-l-yI-thieno[3-c]pyridine-2-sulfonic acid phenefliyl-ainide hydrocWoride The synfiiesis was preformed essentially as described in Method H-L from 4-(2-pheiietliy!sulfanioyl-thieiio[3-c]pyridin-4-yI)-piperazine-l-carboxyHc acid tert-hntyl ester (0.U2 mmoX 1 equiv.). Yield: 3.8 mg. LC/MS: tR= 0.410 {Systran: 30% to 60% ACN in 1.5 min, YMC), Purity: 91 %. MS: 403 (M+1) 'HNMR(270MHz, CH30H-d4) 5ppm 1.44 (d, 7.13 Hz, 2 H) 3.51 (d, J=4.75 Hz, 4 H) 3.54 (s, 2 H) 3.94 (m, 4 H) 7.05 (m, 4 H) 7.16 (m, I H) 7.62 (s, 1 H) 7.72 (d, 7=6.60 Hz, 1 H) 8.00 (d, 7=6.60 Hz, 1 H). EXAMPLE 71 4-i'iperaziD-l-yI-thieno[3]pyridine-2-siilfoiiic acid (2,6-diethyl-pheny!)-amide hydrochloride The synthesis was prefonned essentially as described in Method H-L from 4-[2-(2,6-dethyl-phenylsulfamoyI)-thieno[3,2-c]pyridin-4-yl]-piperazine-l-coxyIic acid (ert-butyl ester (0.112 mraol, 1 equiv.). Yield: 9.0 mg. LCVMS: tR= 0.830 (System: 30 % to 60 % ACN in 1.5 min, YMQ, Purity: 92 %. MS: 431 (M+1) 'H NMR (270 MHz, DMS0-D6) 5 ppm 0.96 (t, 7.52 Hz, 6 H) 2.25 (m, I H) 2.43 (s, 2 H) 2.75 (t, 7=1.72 Hz, 1 H) 3.26 (s, 4 H) 3.62 (s, 4 H) 7.09 (s, 1 H) 7.12 (s, 1 H) 7.23 (m, 1 H) 7.73 (d, 5.81 Hz, 1 H) 7.77 (s, 1 H) 8.19 (d,7=5.81Hz, 1 H) 9.04(s, 1 H) 9.95 (s, 1H). EXAMPLE 72 4-Plperaziii-l-yl-ttieno[3clpyridine-2-snlfonic acid (3-pIieayl-propyI)-anude hydrochloride The synthesis was preformed rasentially as described in Method H-L from 4-[2-(3-phenyl-propylsiilfainoyl)-thieno[3,2-c]pyridin-4-yI]-piperazine-l-cart)ox)dic acid teri-hutyl ester (0.112 mmol, 1 equiv.). Yield: 13.0 mg. LC/MS: tR= 0.726 (System: 30 YD to 60 % ACN in 1.5 min, YMC), Purity: 91 %. MS: 417 (M+1) 'H NMR (270 MHz, CH1OH-df) 6 ppm 1.82 (m, 2 H) 2.63 (m, 2 H) 3.04 (t, 7=6.86 Hz, 2 H) 3.55 (s, 4 H) 4.09 (s, 4 H) 7.16 (m, 4 IQ 7.82 (d, 6.60 Hz, 1 H) 8.05 (d, 7=6.33 Hz, 1 H) 8.14 (s, 1 H). EXAMPLE 73 4-Piperazm-l-yl-tIiieno[3c]pyridine-2-siiIfonlc acid (S-dipheoyl-propylj-ainide hydrochloric acid The synthesis was preformed essentially as described in Method H-L fiom 4-[2-(3,3-diphenyl-prop)dsulfamoyI)-thieno[3-c]pyiidin-4-yl]i>iperazine-l-carboxylic acid tert-butyl ester (0.112 mmol, 1 equiv.). Yield: 14.4 mg. LC/MS: tR= 1.109 (System: 30 % to 60 % ACN in 1.5 min, YMC), Purity: 93 %. MS: 493 (M+1) 'HNMR(270 MHz, DMSO-de) Sppm2.20 (m, 2H) 2.S0 (m, 2H) 3.29 (s, 4H) 3.67 (d,>5.01 Hz, 4H) 4.01 (m, 1 H) 7.14(m, 8H)7.71 (d,>5.81 Hz, 1 H)7.95 (s, 1H)8.18{d,5.81 Hz, 1 H) 8.27 (m, 2H) 9.13(3,2 H). EXAMPLE 74 4-Pipera-l-yt-thieno[3-cIpyridine-2-snlfonicacid[2-(5-metIioxy-lH-indol~3-yI)-e&yl]-amide hydrochloride The synthesis was preformed essentially as described in Method H-L from 4-{2-[2-(5-methoxy-1 H-mdol-3-yI)-ethyisulfamoyl]-thieno[3,2-c]pyridin-4-yl} -piperazine-1-carboxylic acid (ert-butyl ester (O.I 12 mmol, 1 equiv.). Yield; 6.1 mg. LC/MS: ta= 0.364 (System: 30 % to 60 % ACN in 1.5 min, YMC), Purity: 91 %. MS: 472 (M+1) 'HNMR (270 MHz, CH30H-d4) & ppm 2.85 (t, J.20 Hz, 2 H) 3.48 (t, >6.20 Hz, 2 H) 3.55 (m, 4 H) 3.80 (s, 3 H) 4.02 (m, 4 H) 6.44 (dd, >8.71,2.37 Hz, 1 H) 6.80 (m, 2 H) 6.97 (s, 1 H) 7.64 (s, 1 H) 7.67 (s, 1 H) 7.97 (d, ..60 Hz, 1 H). EXAMPLE 75 4-Piperaziii-l-yI-tliieno[3,2-c]pyridine-2-saIfonicacid4-trinuoromethyI-ben2ylaiiiide hydrodtloride The synthesis was prefonned essentially as described in Method H-L fiom 4-[2-(4-trifluoronietiiyl-bajzyIsulfemoyl)-thieEo[3,2-c]pyridin-4-yl]-piperazine-l-caiboxyHcacid tej-f-butyi ester (0.112 nunol, 1 equiv.) was used as the thienopyridine in Method C. Yield: 1.9 mg. LC/MS: tR= 0.771 (System: 30% to 60% ACN in 1.5 min, YMC), Purity: 91%. MS: 457 (M+1) 'H NMR(270 MHz, CH1OH-di) 5 ppm 3.54 (m, 4 H) 3.98 (m, 4 H) 4.36 (s, 2 H) 7.49 (m, 4 H) 7.74 (d, ..86 Hz, 1 H) 8.02 (s, 1 H) 8.07 (d, /=6.60 Hz, 1H). EXAMPLE 76 4-Feraziii-l-yl-IMeito[3-clpyiine'2-$ii]fonic acid beitzyl-efltyl-aiiade hydrochloride The synthesis WM prefbrmed essOTtially as described in Method H-L from 4-[2-(beiizyl-ethyl-sulfamoy!)-thieQo[3,2-c]pyridE[i-4-yl]-pipera2ine-l-carboxylic acid/ert-butyl ester (0.112 nunol, 1 equiv.). Yield: 6.4 mg. LC/MS: tR= 0.930 (Systran: 30 % to 60 % ACN in 1.5 min, YMC), Purity: 95 %. MS: 417 (M+1) HNMR (270 MHz, CH1OH-d,) 5 ppm 1.03 (t, J=7.13 Hz, 3 H) 3.37 (m, 2H) 3.57 (s,2H) 3.75 (m, 2 H) 4.11 (s, 2 H) 4.50 (s, 2 H) 5.80 (s, 1 H) 7.32 (m, 5 H) 7.84 (d,.=6.60 Hz, 1H) S.07 (d, ..60 Hz, 1 H) 8.14 (s, 1 H). INTERMEDIATE 55 tert-ButyI-4-(3-{[(3-ethylpheiiyI)amino|snifony!}fliieno[3]pyridin-4-yl)piperaziHe- l-i»rborylate Prated ftom (eM-butyl 4-[3-(ohlorQsulfouyl)thieno[3,2-c]pyridin-4-yl]pipa:az!iie-i-carboxylate (90.0 mg, 0.215 romol) and 3-ethylamline (33.9 mg, 0.28 mmol) to give the title compound as an off-white solid (82.7 mg, 76 %), H NMR (400 MHz, CDCli) 5 1.03 (t, J = 7.5 Hz, 3 H), 1.48 (s, 9 H), 2.47 (q, J = 7.7 Hz, 2 H), 3.00-3.53 (m, 6 H), 4.02-4.44 (in, 2 H), 6.66 (d, J = 8.0 Hz, 1 H), 6.75 (s, 1 H), 6.66 (d, J = 8.0 Hz, 1 H), 7.02 (t, J = 7.8 Hz, 1 H), 7.67 (d, J = 5.5 Hz, 1 H), 8.24 (s, 1 H), 8.39 (d, J = 5.5 Hz, 1 H), 9.80 (s, 1 H). MS (ESI+) m/z 503.2 (M+H)*. HPLC 97 %, RT: 3.93 min (5-99 % MeCN over 3 min). EXAMPLE 77 N-(3-EthyIpheiiyI)-4-piperazin-l-yJailenol3,2-clpyridine-3-snlfoiiaiiiidehydrochlonde Prepared from ?err-butyl 4-(3-{[(3-ethylphenyl)aniino]su]fonyI}thieno[3,2-c]pyridin-4-yl)piperazine-l-caihoxylate (81.1 mg, 0.161 mmol) which afforded 19 mg (98 %) of the product as a white soHd (38.0 mg, 54 %). 'H NMR (400 MHz, CH1OH-dfl) 5 1.09 (t, J= 7.5 Hz, 3 H), 2.51 (q, /= 7.5 Hz, 2 H), 3.59 (br.s, 8 H), 6.89-6.92 (m, 3 H), 7.12-7.14 (m, 1H), 8.06 (d, y = 6.0 Hz, 1 H), 8.36 (d, /= 6.0 Hz, 1 H), 8.49 (s, 1 H). MS (ESI+) m/2 403.2 (M+H) HPLC 95%, RT: 3.02 min (5-99% MeCNover3 min). INTERMEDIATE 56 tert-Butyl4-C3-bromothieno{3;2-c]pyridin-4-yI)piperazuie-l-carboxylate Amixture of 3-brolno-4-chlorothieno[3,2-c]pyridine (729 mg, 2.93mmol), tert-hntyi piperazine- 1-carboxyIate (1.64 g, 8.S0 mmo]) and K2CO3 (811 mg, 5.87 mmol) in DMSO (45 mL) was stirred for 5 days at 100 °C. After addition of H2O and ethyl acetate, the layers were separated. The waterphase was extracted twice with ethyl acetate, and the combined organic phases WKC washed with water and brine and dried QAgSOi). After filtration and removal of the solvent, fhe residue was purified by silica gel f! chromatogTiIiy (pentane/eQiyl acetate, S:2) to give the product as a white powder (398 mg, 34 %). HPLC 99%, RT: 3.27 min (5-99% MeCN over 3 min).H NMR (400 MHz, CH30H-d4) S 1.48 (s, 9 H), 3.21 (br.s, 4H), 3.71 (sbr., 4H), 7.61 (d, J= 6.1 Hz, 1 H), 7.72 (s, 1 H), 8.08 (d, J= 5.6 Hz, 1 H). MS (ESI+) m/z 398.2 (M+H)*. INTERMEDIATE 57 {4-[4-((ert-Batoxycarbonyl)piperaziB-l-yl]thieDo[3,2-clpyridin-3'yl}sulfonyI)Utliiiim To a suspension of tert-Butyl 4-(3-bromofliieno[3,2-c]pyridin-4-yl)piperazme-l-carboxylate (4.055 g, 10.18 mmol) in diethyl ether (30 mL) at -78 "C under N2 almosphere was added dropwise an 1.6 M solution of n-BuLi ia hexanes (9.5 mL;. 15.2 mmol). After 1 h of stirring, a saturated solution of SO2 in THF (25 mL) at -78 °C was transferred via a camiula to the mixture. The reaction was allowed to gradually increase to ambient temperature over night. The solvent was evaporated, and ftie residue was washed wifli several portions of diethyl ether and then dried under vacuum to ve 4.094 g of an off-white solid consisting of 66 % of the title compoimd and 34 % of {«~b«tylsulfonyl)lithiuni as by-product This mixture was used without any fiirtha- purification in the next step. 'H NMR (400 MHz, CHsOH-d*) S 1.48 (s, 9 H), 3.22 (far.s, 4 H), 3.72 (s far., 4 H), 7.60 (d, J= 5.5 Hz, 1 H), 8.06 (d, J= 5.5 Hz, 1 H), 8.14 (s, 1 H). MS (ESH-) ra/z 384.0 (M+H)"". HPLC RT: 2.62 min (5-99% MeCN over 3 mio). INTERMEDIATE 58 reit-Buty!-4-[3-(chlorosiilfonythienop-c]pyridm-4-yI]piperaziBe-l-carboxyIate To a suspension of ({4-[4-(;ert-bittoxycarbonyl)piperazin-l-jl]thieno[3-c]pyridin-3-yl}sulfonyl)haiiiim (2.751 g, 7,06 mmol (3.126 g of the crude product mixhire)) in DCM (40 mL) at 0 °C was added A'-chlorosuccimmide (1.338 g, 10.0 mmol). After 20 minutes, the tempa:ature was raised to ambient, and the reaction mixture was stirred for an additional 2.5 h. The resulting product solution was washed with water, and the water phase was extracted with DCM. The combined co-ganic extracts were waed with brine and dried over MgSO*, Aiter filtration and evoration of the solvent, die residue was washed with several porticms of pentaae to yield the product as an ofF-wbite solid (2.024 g, 69 %), MNMR(400MHZ, CHsOH-di) 5 1.47 (s, 9 H), 3.11 (br.s, 4H), 3.2-4.3 (sbr., 4 H), 7.68 (d, y= 5.5 Hz, 1 H), 8.45 (d, /= 5.5 Hz, 3 H), 8.60 (s, 1 H). MS (ESI+) TK/Z 418.2 (M+H)"", HPLC 92%, RT: 3.76 min (5-99% MeCN over 3 min). INTERMEDIATE 59 te«-BnfyI-4-(3-{[(4-isopropyIphenyI)ainiiio]sulfonyl}thieno[3,2-cIpyridin4- yl)piperazine-l-carboxylate Prepared from tert-hntyl 4-[3-(chIorosuIfonyl)fhieno[3-c]pyridin-4-yI]piperazine-l-carboxylate (90.0 mg, 0.215 mmo!) and 4-isopropylamline (37.9 mg, 0.28 mmol) to give the title compound as an off-white solid (58.3 mg, 52 %). H NMR (400 MHz, CDCI3) 5 1.12 (d, J= 7.0 Hz, 6 H), 1.47 (s, 9 H), 2.76 (sept, J= 6.9 Hz, 2 H), 3.01-3.53 (m, 6 H), 4.04.41 (m, 2 H), 6.79 (d, /= 8.5 Hz, 2 H), 6.66 (d, J= 8.5 Hz, 2 H), 7.69 (d, J= 5,5 Hz, 1 H), 8.23 (s, 1 H), 8,40 (d, J= 5.5 Hz, 1 H), 9.90 (s, 1 H). MS (ESH-) m/z 517.2 (M+H)'. HPLC 97%, RT: 4.01 min (5-99% MeCN over 3 min). EXAMPLE 78 N'(4-IsopropyIpheiiyI)-4-piperazin-l-yltbieno[3,2-c]pyrid{ne-3-sDlfoDaiiiide bydrodtbride Prepared from tert-hatyl 4-(3-{[(4-isopropylphenyI)amino]sulfonyl}2ueno[3,2-c]pyridin-4-yl)piperazme-l-carboxylate (60.0 mg, 0.116 mmol) \diich afforded 19 mg (98 %) of the product as a white solid (25.8 mg, 49.%) according to Method H-L. H NMR (400 MHz, CH30H-d4) 8 1.16 (d, J 7.0 Hz, 6 H), 2.81 (st, /= 6.8 Hz, 1 H), 3.59 (s, br., 8 H), 7.00 (d, J= 8.0 Hz, 2 H), 7.10 (d, /= 8.0 Hz, 2 H), 8.07 (s, br., 1 H), S.37 (s, br., 1 H), S.50 (s, 1 H). MS {ESI+) m 417.2 (M+H)*. HPLC 94%, RT: 3.14 min (5-99% MeCN over 3 min). EXA2vIPLE79 N-(4-MethyIp&enyl)-4-(pyrroUdm-3-yloxy)tliieiio[3-c]pjTidine-2-siilfoHainide bydrocbloiide 4-CMoro-A'-(4-inetbylpheiiyI)thieno[3,2-c]pyridme-2-sul&naiiude (60.0 mg, 0.17 nimol) in diy DMF (1 mL) and NaH (5,1 mg, 0.21 mmol) was added to pyrrolidJn-3-oI (18.5 mg, 0.21 mmol) uuder nittogai. The mixtiiie was heated in the microwave at 200°C in 5 min. The product was purified by prarative HPLC. Yield: 29.9 mg (43.4 %). 'H NMR (270 MHz, CH1OH'dj) S ppm 8.09 (s, IH) 7.71 (d, >6.93 Hz, 1 H) 7.46 (d, 7=6.93 Hz, I H) 7.47-7.44 (m, 4H) 4.67 (d, >3.22 Hz, 1 H) 3.97 (s, 1H) 2.26 (s, 3H>. LC-MS 390 (M -H)*; Purity (HPLC) 99%. EXAMPLE 80 N-(4-MethylphenyI)-4-(piperidin-4-yloxy)tMeDo[3c]pyridiiie-2-snIfonainide hydrochloride The synthesis was preformed Ksenally as described for compound of N-{4-methylphemyI)-4-(pyrro]idin-3-yIoxy)thieiio[3,2-c]pyridme-2-suIfcttiamid6 hydrochloride. Yield: 16.2 mg (22.7 %). 'H NMR (270 MHz, CH1OH-Kif) 5 ppm 7.81-7.78 (m, 2H) 7.62 (d, >6.93 Hz, 1 H) 7.13-7.04 (m, 4H) 4.05-3.94 (m, IH) 3.90-3.88 (m, 2H) 3.63-3.58 (ro, 2H), 2.27 (s, 3H) 2.Q6-2.03 (m, 2H) 2.01-I.7I (m, 2H); LC-MS 404 (M - H);Purity (HPLC) 99 %. EXAMPLES! N-(2,3-Difluoroben2yI)-4-piperazin-l-jdthieno[3-c]pyridme-2-siilfoDamide hydrochloride Yield: 74,4 mg (39,2 %). 'H NMR (270 MHz> CH1OH-d) 5 ppm 8.10-8.03 (m, 2H) 7.S1 (d, /=6.68 Hz, 1 H) 7.16-7.05 (m, 3H) 4.37 (s, 2 H) 4.11-4.07 (m, 4H) 3.59-3.53 (m, 4H); LC-MS 425 (M - H); Purity (HPLC) 90 %. EXAMPLE 82 N-(3-Ch,lorobenzyl)-4-pipera)aii-l-yWiiei!ot3-c]pyridme-2-siilfonaiiiide hydrochloride Yield: 74.4 mg (44.7 %). H MvlR (270 MHz, CH30H-d4) 8 ppm 8.04-8.01 7.85 (d, >6.93 Hz, 1 H) 7.22-7.15 (m, 4H) 4.30 (s, 2 H) 4.14-4.10 (m, 4H) 3.60-3.54 (m, 4H); LC-MS 423 (M - H); Purity (HPLC) 90%. Legend lo Scheme 6: i) BOC protected ammes (R*), KaCOj, DMSO; u) aiiophenols (R'-SH). CafTjO, DMF; iii) NaOAc, oxtme, water; iv) a.TFA, b.HCl, mefliaiio] INTERMEDIATE 60 tert-Batyl4-(2-bromothieDOt3clpyridm-4-yI)piperazine-l-carboxylate 2-Bromo-4-dilorothienop,2-c]pyridme (5.0 g, 20.24 mmol) and KCOs (13.97 g, 101.2 mmol) was stSired is DMSO (20 mL) followed by addintion of teri-hutyl piperazine-l-caiboxylate (4.14 g, 22.26 mmol). The reaction mixture was stirred at 100 °C for 6 days. The reaction mixture was filtered io eliminate fee caibonate and addition of water (50 mL) and ethyl was followed. The phases were sarated and flie aqueous phase was extracted with ethyl acetate. The combined organic phases were dried (MgS04) and the solvait was evorated. The crude pioduct was purified by flash chromatography using ethyl acetate/hexanes (2/8) as eiuent to give 2 g of the desired product, yield 25%, 99% pure. 'H NMR(270MHz,CDCl3)5 1.48 (s,9H), 1.52-1.63 (m, IH), 3.42-3.47 (m,4H), 3.61-3.64 (m, 4H), 7.22 (dd, J= 5.4,1 Hz, IH), 7.35 (d. J= 1 Hz, IH), 8.04 (d, J= 5.4 Hz, IH). m/z = 398.91 (M+H), bromide pattern. INTERMEDIATE 61 (ert-butyl4-(2-bromottieno[3>2-c]pyridiii-4-yl)-lv4-diazepane-l-carboxylate The same procedure above intmediate was used starting from 2-bromo-4-chlorothieno|;3,2-c]pyriifine (7.5 g, 30.45 mmol), KzCOj (6.7 g, 33.5 mmol) and fert-butyl 1,4-diazepane-l-carboxylate (21.0 g, 152.2 imnol) in DMSO (30 mL). Purification by flash chromatography 3.04 g of tiie title compound (Yield 25%)ilPLC purity 92%; 'H NMR (270 MHz, CDCI3) & 1.38 (s, 4.5 H), 1.43 (s, 4.5 H), 1.96-2.11 (to, 2H), 3.36-3.41 {m, IH), 3.46-3.51 (m, IH), 3.65-3.S7 (m, 6H), 7.02-7.04 (m, IH), 7.40-7.42 (m, IH), 7.94 (d, J= 5.4Hz, lH).m/z =411.97 (M+H). Coupling vfith thiophenols (Method M ) INTERMEDIATE 62 teM-butyI4-(2-pbenylthio)thieiio[3-c]pyridin-4-yI)-l,4-diazepane-l-carboxylate *er!'Buty]4-(2-'bromc.thimoi3,2-c3pyridin-4-yl)-l,4-diazepaae-l-carboxyia.te (0.31 g, D.752 mmol), pulverized KOH (0.084 g, 1.5 mmol) and Cu2(I)0 (0.1 g, 0.75 mmol) was aiixed wifli DMF (1 mL) before the addition of a solution of benzenethiol (.016 g, 1.5 mnol) in DMF (1 mL). Tte reaction mixture was heated to 120 °C for 15 h. The reaction nixtUTB was poured in a silica plug and eluted with chloroform, to give the crude product, the crude product was purified by flash chiomatogrhy using efliyl acetate/hexanes (2/8) ts eluent to give 0.21 gofthedesiredproduct, yield 64%, 90% pure. 'H NMR (270 MHz, :X>Ch) 5 1.37 (s, 4.5H), 1.43 (s, 4.5 H), 1.97-2.10 (m, 2H), 3.36-3,43 (m, IH), 3.46-3.53 m, IH), 3.64-3.73 (m, 2H), 3.78-3.96 (m, 4H), 7.05 (d, J= 5.4 Hz, IH). 7.22-7.32 (m, 5H), '.59-7.63 (m, IH), 7.97 (d, J= S.4 Hz, IH). m/z = 442.15 (M+H). >xidation of thuHderlvatives (Method N) MTERMEDLVTE 63 3rt-Butyl4-P-pheny]snIfonyI)thieiio[3]pyridin-4-yrHl,4-diazepane-i-carbo3£ylate L solution of tert-Butyl 4-(2-phenyithio)ttueno[3,2-c]pyridin'4-yl)-l,4-diazepane-l-srboxyiate (0.21 g, 0.48 omiol) and NaOAc (0.5 g) in ethanol (10 mL), (pH ~5) followed y ae addition of Oxone (0.64 g, 1.04 mmol) dissolved m water (1 mL). The reaction mixture was stured at RT for 15 h. Aditional Oxone (0.32 g) in water (ImL) was added. Full conversion of the SM was obtained after 8 h. Wata: (50 mL) and chloroform (30 mL) were added. The phases were separated and die aqueous phase was extracted with chlorofbnn. The combined organic phases were dried over (MgS04), the solvent was evaporated to give the crude product which was purified by reverse-phase chromatography (10-?-90), to give 0.191 g of the desired product as yellow oil (Yield 86%) 98% pure. 'H NMR (270 MHz, CDCI3) 5 1.28 (s, 4.5 H). 1.38 (s, 4.5 H), 1.99-2.03 (m, 2H), 3.31-3.40 (m, IH), 3.42-3.47 (m, IH), 3.63-3.69 (m, 2H), 3.85-3.98 (m, 4H), 7.02 (d, J= 5.4 Hz, IH), 7.48-7.61 (m, 3H), 7.76-8.01 (m, 3H), 8.06-8.08 (m, IH). m/z = 474.01 (M+H). Removal of the bntyl-carboxylate protecting group (Method O) EXAMPLE 83 4-(l,4-Diazepan~l-yI)-2-(phenylsu!fonyr)thieDo[3c]pyri(Une hydrochloride ieM-Butjd4-(2-phenyIsulfonyI)thieno[3,2-c]pjTidin-4-yl)-I,4-diazepane-l-caiboxylate (0.165 g, 0.348 mmol) was dissolved in DCM (2 mL) and TFA (1 mL) was added. The reaction mixture was stirred for 2 h. The solvent was eviorated. Methanol and HCl in ether was added (x 3) to give 0.118 g of ttie desired HCl salt, yield 85%, 98% pure. 'H NMR (270 MHz, CHOH-dj) 5 2.45-2.52 (m, 2H), 3.45-3.52 (m, 2H), 3.70-3.79 (m, 2H), 4.18-4.22 (m, 2H), 4.30-4.40 (m, 2H), 7.62-7.76 (m, 5H), 7.91 (d, J = 5.4 Hz, IH), 8.11 (dd, J= 5.4,1 Hz, IH), 8.41 (d, J= 1 Hz, IH). m/z= 374.09 (M+H-HCl). INTERMEDLiTE 64 tert-ButyI4-[2-(4-tert-biitylpIienyI)thio]aiieno[3clpyridin-4-yl)-l,4-diazepane-l- carboxylate The product was prared according to Method M. Purification by flash chromatography using ethyl acetate/hexaues (2/8) as eluent gave 0.035 g, 99% pure. 'H NMR (270 MHz, CDCI3) 5 1.28 (s, 9H), 1.38 (s, 4.5 H). 1.43 (s, 4.5 H), 1.98-2.03 (m, 2H), 3.35-3.41 (m, IH), 3.46-3,52 (m, IH), 3.62-3.72 (m, 2H), 3.77-3.93 (4H), 7.04 (d, J= 5.4 Hz, IH), 7.27-7.34 (m, 4H), 7.54-7.56 (m, IH), 7.95 (d, r= 5.4 Hz, IH). m = 498.0 (M+H). JNTERMBDJATE 65 tert-Bntyl4-[2-(4-/ert-bntylphaiyl)siiIfony!]fl!iei!o[3clpyridm-4-yr)-l,4-diazepane-l- carboxylate Procedure B from (erf-butyl 4-[2-(4-teit-butylphenyl)thio]ttiieno[3 -c]pyridin-4-yl)-l ,4-diazepane-1 -caiboxylate (0.035 g, 0.070 mmolX Oxone (0.17 g, 0.28 mmo]), NaOAc (0.5 g) in EtOH (2 mLfoUowed by reversed phase chromatography (4O->70), gave 6 mg of the product. Yield 17%, 98% pare. HNMR (270 MHz, CDCfe) 51.32 (s, 9H), 1.35 (s, 9H), 2.05-2.15 (m,2H), 3.45-3.62 (in, 2H), 3.75-4.13 (m, 6H), 7,20-7.27 (m, 5H), 7.58 (d, J= ] 0.8 Hz, 1H>, 7.93 (4 J= 10-S Hz, IH). m/z = 530.0 (M+H). INTEEMEDIATE 66 tert-Bntyl4-l2-(3,4-dimethyIplienyI)thiolthieno[3p£-c]pyridin-4-y0-l,4-diazepane-l- carboxylate The title compound was obtained according to Meftiod M. Purification by flash chromatography using efeyl acetate/hexanes (2/8) as eluent gave 0-022 g, 95% pure, 'H NMR (270 MHz, CDCI3) 5 1.38 (s, 4.5 H), 1.43 (s, 4.5 H), 1.96-2.04 (m, 2H), 2.21 (s, 3H), 2.22 (s, 3H), 3.37-3.45 (m, 2H), 3.47-3.50 (m, 2H), 3.77-3.95 (m, 4H), 7.01-7.12 (m, 3H), 7.16 (s, IH), 7.53 (dd, J= 5.4,1 Hz, IH), 7.94 (d, J= 5.4 Hz, IH). m/z = 470.3 (M+H). INTERMEDIATE 67 tert-BuI4-|2-(3,4-dlniethylphenyI)sulfonyI]tIiienoI3c]pyridin-4-yr)-I,4-diazepane- 1-carboxj'late Procedure B from teri-Butyl 4-[2-(3,4-dimethylphenyI)thio]thieno[3,2-c]pyridin-4-yl)-l,4-diazepane-l-carboxylate (0.022 g, 0.047 mmo!); OXOME (0.11 g, 0.19 mmol); NaOAc (0.5 g)iiiEtOH (2 EDL) followed by reversed phe chromatography (40->-70), 9 mg of the product. Yield 38%, 92% piire.'H NMR (270 MHz, CDCI3) 6 1.35 (s, 9H), 2.08-2.20 (m, 2H), 2.33 (s, 6H), 3.52-3.59 (m, 2H), 3.83-3.88 (m, 2Hi, 4.08-4.18 (m, 4H), 7.21-7.2S (m, 2H), 7.31-7.35 (m, !H), 7,73-7.75 (m, 2H), 8.02 (d, J= 5.4 Hz, IH). m/z = 502.21 (M+H). INTERMEDIATE 68 tert-Butyl4-[2-(l-nap6thyI)tMo]1hieno[3-cIpyridiii-4-yl)-l)4-diazepan6-l- carboxylate The title compound was obtained according to Method M. Purification by ilash chromatography using ettiyl acetate/hexanes (2/8) as eluent gave 0.055 g. HPLC purity 99 %; 'H NMR (270 MHz, CTCh) 5 1.37 (s, 4.5 H), 1.43 (s, 4.5 H), 1.89-2.20 (m, 2H), 3.30-3.40 (m, IH), 3.43-3.50 (m, IH), 3.60.3.90 (m, 6H), 6.99 (d, J= 5.4 Hz, IH), 7.39 (dd, J= 8.1,1 Hz, IH), 7.50-7.61 (m, 5H), 7.79-7.SS (m, 2H), 7.92 (d, J= 5.4 Hz, IH), 8.40-8.44 (m, IH). rn/z = 498.26 (M+H). INTERMEDIATE 69 tert-Butyl4-[2-(l-naphfliy0snlfonyl]fliieno[3,2-clpyridm-4-yl)-l,4-diazepaBe-l- carboxylate Procedure B from tert-Butyl 4-[2-(l-nhthyl)thio]thieno[3,2-c]pyridin-4-yl>l,4-diazepane-1-carboxylate (0.055 g, 0.112 nimol); Oxone (0.27 g, 0.448 mmol); NaOAc (0.5 g) in EtOH (2 mL) followed reversed phase chromatogrhy (40->70) gave 15 mg of the product Yield 26%, 93% pure. 'H NMR (270 MHz, CDCh) 8 1.34 (s, 9H), 2.06-2.10 (m, 2H), 3.48-3.62 (m, 2E), 3.78-3.86 (m, 2H), 3.95-4.16 (m, 4H), 7.19-7.31 (m, 2H), 7.60-7.75 (m, 3H), 7.92-7.99 (m, 2H), 8.18 (m, 1= 8.1 Hz, IH), 8.50-8.53 (m, IH), 8.77-8.80 (m, IH). m/z = 524.22 (M+H); EXAMPLE 84 4-(l,4-Dla2epan-I-yI)-2-[(3,4-dichloropIienyl)suIfonyl]thieno[3]pyridine hydrochloride fert-Butyl4-{2-[(3,4-dich!orophenyI)sulfonyl]thiKio[3,2-c]pyridin-4-yl}-l,4-diazepane-i. carboxylate was prepared &om 3,4-dichlorothiophenol (60 mg, 15%), as a beige solid, by the application of the general procedure A and B described above. 'H NMR (CDCb) S 8.27-8.14 (m, IH), S.11-8.04 (m, 2H), 7.87-7.80 (m, IH), 7.67-7.62 (m, IH), 7.26-7.20 (m, IH), 4.18-3.9S (m, 4H), 3.87-3.74 (m, 2H), 3.61-3.44 (m, 2H), 2.20-2.00 (m, 2H), 1.33 (s, 9H); MS m/z 542 CM+l).The title compound (50 mg, 95%) was obtained as a beige solid, by the plication of the general procedure C described above. H NMR (270 MHz, CH1OH-d*) d 8.48 (s, IH), 8.30 (d, J-1.85 Hz, IH), S.05 (dd, /= 8.58,1.98 Hz, IH), 7.92 (d, J= 6.86 Hz, IH), 7.83 (d, /= 8.44 Hz, IH), 7.69 (d, /= 6.86 Hz, IH), 4.4.41-4.34 (m, 2H), 4.24-4.16 (m, 2H), 3.76-3.69 (ra, 2H), 3.51-3.43 (m, 2H), 2.52-2.42 (m, 2H); MS Wz442(M+l). EXAMPLE 85 4-(l,4-Diazepaa-l-yI)-2-[l-naphthylsHifonyI)ttdeflo[3,2-clpyriiIIne hydrochloride The title compound was obtamed from ieM-butyl 4-[2-(l-n£h1iiyI)sulfoiiyl]thieno-[3,2-c]piTidm-4-yl)-l,4-diazepane-l-carboxylate(15 mg, 0.029 mmol) following Method O to give 12 mg of the desired product yield 90 %, 95 % pure. 'H NMR (270 MHz, CH30H-d4) 6 2.40-2.50 (m, 2H), 3.45-3.55 (m, 2H), 3.65-3.75 (m, 2H), 4.06-4.26 (m, 2H), 4.27-4.46 (m, 2H), 7.58-7.80 (m, 4H), 7.83-7.86 (m, IH), 8.06 (d, J= 8.1 Hz, IH), 8.20 (d, J= 8.1 Hz, IH), 8.48 (s, IH). 8.53-8.56 (m, IH), 8.83-8.86 (m, 1). mJz = 424.06 (M+H-HCl). EXAMPLE 86 4-(l,4-Diazepaii-i-yI)-2-[4-/'e«'-butylplienylsulfonyl)thieno[3]pyridine hydrochloride The title compound was obtained from (ert-butyl 4-[2-(4-tert-butyIphenyl)-sulfbnyi]thieno[3,2-c]pyridin-4-yl)-l,4-diazcpane-l-carboxylate(6ing, 11.3 mmol) following Method O to give 4 mg of the desired product, yield 76 %, 88 % piire. 'H NMR (270 MHz, CHaOH-dj) 5 1.33 (s, 9H), 2.41-2.47 (m, 2H), 3.41-3.49 (m, 2H), 3,65-3.78 (m, 2H), 4.15-4.25 (m, 2H), 4.29-4.40 (m, 2H), 7,65-7.70 (m, 3H), 7.90 (d, J= 5.4 Hz, IH), 8.00-8.04 (m, 2H), 8.37 (s, IH). m/z = 430.06 (M+H- EXAMPLE87 4-(I,4-DiazepaB-l-yl)-2-{3,4-dimethyIpbenylsaIfonj1)thieno[3]pyridine hydrochloride The title compound was obtained from tert-butyl 4-[2-(3,4 dimethylphenyl)-sulfonyi]aiieno[3,2-c]pyridin-4-yl)-l,4-diazepane-l-carboxyIate (6 mg, 0,012 mmo!) following Method 0 to give 6 mg of the desired product, yield 88 %, 89 % pure. 'H NMR (270 MHZ, CH30H-d4) S 2.34 (s, 6H), 2.45-2,55 (m, 2H), 3.42-3.51 (m, 2H), 3.67-3.76 (m. 2H), 4.10-4.20 (m, 2H), 3.58-3.70 (m, 2H), 7.39-7.41 (m, 1H>, 7-64-7.67 (m, IH), 7.79-7.84 (m, 2H), 7.89-7.91 (m, IH), 8.36 (s, IH). m/z = 402.07 (M+H-HQ). EXAMPLE 88 2-[(4-BromopheDyI}sulfonyI]-4-(lv4-dtazepan-l-y1)tbieiio[3Ipyridine hydrochloride Triftaoroaceitic acid (1 inL) was added slowly to a solution of tert-butyl 4-{2-[(4-bromopheayJ)thio]thieso[3-c]pyridiB-4-yl}-l,4-diazane-]-carboxylate (26 mg, 0.047 mmol) in CH2Cb at 0 °C. The reaction mixture was allowed to reach room temperature, stirred for 40 min and then concentrated in vacuo. The residue was twice re-dissolved in MeOH and concentrated in vacuo. The rdue was again dissolved in MeOH and an excess of IM HCl in diethyl ether (4 mL) was slowly added to the solution. Removal of Ifae solvents in vacuo afforded the title compound (21 mg, 91 %) as a yellowish solid. H MMR. (270 MHz, CH30H-d4) S 8.41 (s, IH), 8.06-7.99 (m, 2H), 7.92 (d, J= 6.86 Hz, IH), 7.87-7.80 (m, 2H), 7.66 (d, /= 6.86 Hz, IH), 4.38-4.31 (m, IS), 4.22-4.14 (m, 2H), 3.74-3.67 (m, 2H), 3.50-3.42 (m, 2H), 2.51-2.39 (m, 2H); MS m/z 452 (M+I). EXAMPLE 89 2-(PbenyIsnlfonyI)-4-piperazia-l-ylttiieno[3,2-c]pyridine hydrochloride To a stirred solution of fert-butyl 4-[2-(pheiiyIthio)thieno[3,2-c]pyridin-4-yl]piperazine-l-carboxylate (350 mg, 0.819 mmol) in ethanol was added oxone in water solution. The reaction was monitored by LCMS. When all starting material was consumed, tiie chromatogram showed two major peaks, the product and the N-oxide. After purification by prarative HPLC, the resulting Boc-material was treated with HCl in ether. The solution was caifriiiJgated and the supernatant was removed. Ether was added, then centiifegated and decanted (repeated three times) to remove the excess HCl The remaining ether was tinally evaporated in a SpeedVac concentrator. Yield 18 %, HPLC purity = 98%, m/z = 360.0 (M+H). 'H NMR (270 MHz, CHsOH-d*) 8 ppm 3.56 (m, 4 H) 4.08 (m, 4 H) 7.68 (m, 4 H) 7.77 (dd, .>.60,0.79 Hz, 1 H) 8.04 (d, >6.33 Hz, 1 H) 8.12 (m, 2 H) 8.39 (d, >0.79 Hz, 1 H). EXAMPLE 90 2-(3-Methoxy-beiizeitesiilfoayI)-4-piperaziii-l-y)-tliieno[3c]pyridine!iydrocIilor!de 4-[2-(3-Methoxy-phenylsul&iyI)-thieno[3,2-c]pyridm-4-yl]-piperazine-1-carboxylic acid tert-hutyl esta- was obtained from S-methoxythiophraiol (130 |i!, 1 mmol) and tert-Butyl 4-(2-bromo&ieno[3,2-c]pyridin-4-yl)piperazine-l-carboxylat6 (215 mg, 0.52 mmol). 120 mg, 50%) were obtained by the application of flie general Method M described above. 'H NMR (270 MHz, CDCla) S 1.48 (s, 9 H), 3.42-3.51 (iii, 4 H), 3.58-3.67 (m, 4 H), 3.74 (s, 3 H), 6.76 {dd, /=8.18,2.38 Hz, 1H), 6.84-6.92 (m, 2 H), 7.16-7.23 (m, 2 H), 7.51 (s, 1 H), 8.04 (d, >5.81 Hz, 1 H); MS m/z 45S (M+1). The title compound was thefoie obtained flrom 4-[2-(3-meliioxy-phenylsulfenyl)-fliieno[3,2-c]pyridJii-4-yl]-piperazine-l-carboxylic acid iert-butyl (7 mg, 7%), after triturating with diethyl eflier, as a beige solid, by the plication of flie general procedures B and C described above. E NMR (270 MHZ, CD3OD) 6 8.31 (s, IH), 8.09 (d, J = 6.33 Hz, IH), 7.71-7.62 (m, 2H), 7.59-7.50 (m, 2H), 7.30-7.23 (m, IH), 3.98-3.92 (m, 4H), 3.87 (s, 3H), 3.54-3.48 (m, 4H); MS m/z 390 (M+1). EXAMPLE 91 2-(4-Methoxy-benzenesBlfoDy[)-4-pipera2iB-I-yl-tiiieBo[3,2-cIpyridiiie hydrochloride 4-[2-(4-Methoxy-phsiylsulfenyl)-thiaio[3,2-c]pyridin-4-yl]-piperazine-1-caiboxylic acid fert-butyl ester was obtained from 4-raefiioxythiophenol (130 ul, 1 mmol) and tert-butyl 4-(2-bromothieno[3,2-c]pyridJn-4-yl)piperazine-l-carboxylate (215 mg, 0.52 mmol). 100 mg, 42% were isolated by the application of the general Method M described above. HNMR(270MHz,CDClj)5 L48 (s, 9 H), 3.40-3.47 (m, 4 H), 3.58-3.65 (m, 4 H), 3.79 (s, 3 H), 6.83-6.89 (m, 2 H), 7.15 (d, >5.54 Hz, 1 H), 7.35 (s, 1 H), 7.38-7.43 6.33 Hz, IH), 7.17-7.10 (m, 2H), 4.00-3.93 (m, 4H), 3.87 (s, 3H), 3.55-3.48 (m, 4H); MS m/2 390 (M+l), EXAMPLE 92 4-PiperaHB-l-yI-2-{[4-triflnoroiiwthyI)phenyIlsnIfonyl}tliieno[3c]pyridine hydrochloride 2-{[4-(TrifIuoromethyl)phenyl}thiD}-4-pipera2m-l-ylthierio[3,2-c]pyridine (0.42 mmol) was dissolved in TFA (1.5 mL) at 0°C, stirred for 15 min and H2O2 (100 jiL) was added. The mixture was stirred at room temperature over night. NH (2 M) was added, extraction with ethyl acetate (3X), whed with brine, dried over NaS04, The solvent was removed and the product was purified by preparative EPLC to afford 154.7 mg (86.2 %). 'H NMR (270 MHz, DMSO-dfi) 5 ppm 9.79 (s, IH) S.56 (s, I H) S.35 (d, /=8.44 Hz, 2 H) 8.12-8.05 (m, 3H)7.79 (d,>6.33 Hz, 1 H) 3.98-3.96 (m, 4H) 3.32-3.31 (m,4H); LC-MS 428 (M - H)""; Purity (HPLC) 95% EXAMPLE 93 2-[[2-tert-ButyIphenyl)siilfoHy!]-4-piperazui-i-yIthieno[3c]pyridhie hydrochloride The title confound was prepared following Method M-0. Yield: 10.6 mg (6.3 %) of 2-[[2-ierNbutylphenyl)sulfonyl]-4-piperazin-l-)dthieno[3,2-c]pyridine hydrachloride. H NMR (270 MHz, DMSO-di) 5 ppm 9.57 (s, 1 H) 8.42 (s, 1 H) 8.26-8.22 (m, IH) 8.06-8.04 (m, IH) 7.6S-7.55 (m, 4H) 3.87-3.86 (m, 4H) 3,34-3.33 (m, 4H) 1.51-1.43 (m, 9H); LC-MS 400 (M - H)*; Ptirity (HPLC) 90%. EXAMPLE 94 2-p,4-DichIorophenyOsHlfOTylJ-4-piperaziii-3-y]tbJeno[3,2-€]pyridiBe-2-siilfonaniide hydrochloride The title compomd was prepared following Method M-0. Yield: 47.9 mg (22.9 %). H NMR (270 MHz,DMSO-d6) 6ppm 9.36 (s, 1 H) 8.51 {s, 1 H) 8.38 (d,/=2.U Hz, 1 H 8,06-7.94 (m, 3H) 7.70-7.68 (m, IH) 3.81-3.77 (m, 4H) 3.31-3,29 (m, 4H); LC-MS 427 (M -H)*; Purity (HPLC) 95%. EXAMP1395 2-[{4-/ert-Butylpheny0siUfonyl]-4-pipera2iB-l-ylthieno[3,2-c]pyridine hydrochloride Oxone (0.52 g, 0.S4 mmol) in water (4 mL), buffered to pH -~ 6 with sodium oxide acetate, was added to 2-[(4-/ert-biitylphenyI)thio]-4-piperazia-l-yltbieno[3,2-c]pyridi]ie (0.42 mmol) in ethanol (30 mL). The mixture was stirred in room temperature for 2 h and more oxone (0.52 g, 0.84 mmol) was added. The reaction w stirred over night. Water was added to the mixture, extraction wife dichloromethane (2X 20 mL) and the solvent was removed. TTie products were purified by prqiaiative HPLC. Yield: 41.9 mg (22.0%). 'H NMR (500 MHz, CH30H-d4) 5 ppm 8.38 (s, 1 H) 8.05-8.01 (m, 3H) 7.S0 ( EXAMPLE 96 2-(l-NaphthylsaIfonyI)-4-piperazin-l-ylthieno[3c]pyridiBe hydrochloride The title compound WM prepared following Method M-0. Yield: 3,4 mg (0.2 %). 'H NMR (270 MHz, DMSO-de) S ppm 9.34 (s, 1 H) 8.82 (s, 1 H) 8.44 (s, 1 H) 8.26-8.06 (m, 5H) 7.79-7.55 (m, 3H) 3.79-3.78 (m, 4H) 3.32-3.30 (m, 4H); LC-MS 410 QA - H)""; Purity (HPLC) 95%. EXAMPLE 97 2-[(3-FJuorophenyl)siilfoQy-4-pipera2iii-l-ylthieno[3,2-cJpyridine-2-snifonamide hydrochloride 2-Bromo4-ch]orothieno[3,2-c]pyridiiie (190 mg, 0.50 mmol) in DMF (1 mL) was added to 3-fluoTObenzenethiol (95.5 mg, 1.0 mmoi), KOH (56 mg, 0.2 mmol) and CuiO (71 mg, 0.5 mmol) in DMF (ImL), The reaction was heated to UCC over night The mixture was filtrated through a silica plug and the solvent was removed. The product was dissolved in TFA (1.5 mL) at OC and the solution wei stirred for 15 min, H3O2 (100 nL) was added and the mixture was stirred at room tKnpa'ature over nit 2M NaOH was added, extraction with etylacetate, washed with brine and solvent was ranoved. The product w purified by preparative HPLC. Yield: 30.1 mg (16.1%) 'H NMR (270 MHz, DMSO-ds) 6 ppm 9.34 (s, 1 H) 8.45 (s, 1 H) 8.16 (d, /=5.69 Hz, 1 H) 7.97-7.93 (m, 2H) 7.76-7.62 (m. 3H) 3.30 (s, 4 H) (4H obscured by solvent signal); LC-MS 378 (M - H)*; Purity (HPLC) 99%. EXAMPLE 9S 2-(MesitylsnlfonyI)-4-piperaziii-l-ylthieiio[3lpyridinehydroctloride The title compound was prqjared following Method M-0. Yield: 32.0 mg (16.1 %). H NMR(270MHz, DMSO-dg)5ppm9.32 (s, 1 H) 8.20-8.14 (m, 2H) 7.66 (d,5.69Hz, 1 H) 7.14 (s, 2 H) 3.29 (s, 4 H) 2.65 (s, 6H) 2.28 (s, 3H) (4H obscured by solvent signal); LC-MS 402 (M - H)""; Purity (HPLC) 95%. EXAMPLE 99 2-[(2-MeaoxypIieiiyI)siilfonyI]-4-piperiiziB-l-yltbieDo[3,2-c]pyridine]iydrDch]OTide The title compound was prepared following Method M-O.Yield: 14.7 mg (7.6 %). 'H NMR (270 MHz, DMSO-ds) 6 ppm 9.33 (s, 1 H) 8.24 (s, 1 H) S.I5 (d, J=5.94 Hz, 1 H) 8.00 (dd, 7.92.1.48 Hz, 1 H) 7.77-7.68 (m, 2H) 7.28-7.18 (m, 2H) 3.30 (s, 4H) (7H obscured by solvent signal); LC-MS 390 (M - H)'lty (HFIC) 99%. EXAMPLE 100 2-|{2,4-Dimethoxypheiiyl)siilfonyI]-4-piperazm-l-ylthieno[3]pyridine hydrochloride The title compound was prepared following Method M-0. Yield: 42.7 mg (20.5 %). 'H NMR (270 MHz, DMSO-de) S ppm9.39 (s, 1 H) 8.37 (s, 1 H) 8.13 (d, /=5.69 Hz, 1 H) 7.68-7.66 (m, 2H) 7.54 (d, J=2,23 Hz, 1 H) 7.19 (d, /=8.66 Hz, 1H) 3.29 (s, 4 H) (lOH obscured by solvent signal); LC-MS 420 (M - Hf; Purity (HPLC) 98%. EXAMPLE 101 2-[(2,4-Dunefliy!pfieByl)siUfonyI]-4-piperazin-l-yMiieno[3-cIpyridiBe hydrochloride The title compound was prepared following Method M-O. Yield: 17.8 mg (9.3 %). H NMR(270 MHz, DMSO-dg) 6 ppm 9.32 (s, IH) 8.27 (s, 1 H) 8.15 (d, 5.94 Hz, 1 H) 8.00 (d, 7=8.17 Hz, 1 H) 7.67 (d, >5.94 Hz, 1 H) 7.35-7.26 (m, 2H) 3.29 (s, 4H) 2.34 (s, 3H) (7H obscured by solvent signal); LC-MS 38S (M - H)"'Purity (HPLC) 98%. EXAMPLE 102 2-{(2-DimethyIpIieiiyI)sulta)iyI]-4-pipera-l-ylthieno[3c]pyri The title coDound was prepared following Method M-0. Yield: 16.9 mg {8,8 %). H NMR (270 MHz, DMSO-ds) 5 ppm 9.17 (s, 1 H) 8.29 (s, I H) 8.18-18.15 (m, IH) 7.94 (s, 1 H) 7.66 (d, 5.69 Hz, 1 H) 7.47 (d, J=7.67 Hz, 1 H) 7.32 (d, /=8.16 Hz, 1 H) 3.29 (s, 2 H) 2.42 (8, 3 H) (7H obscured by solvent signal); LC-MS 388 (M - ilf; Purity (HPLC) 99%. EXAMPLE 103 2-[(2-Ethylphenyl)siilfonyI]-4-piperazm-l-y!tlileiio[3c]pyri*ne hydrochloride The title compound was prepared following Method M-0. Yield: 22.6 mg (11.2%). H NMR(270MHz,DMSO-d*) 5ppm 9.19 (s, 1H) 8.32 (s, 1 H) 8.17 (d, J=5.69Hz, 1 H) 8.08 (d, >7.92 Hz, I H) 7.73-7.66 (m, 2H) 7.52 (t, =7.67 Hz, 2 H) 3.29 (s, 4 H) 3.00 (q, >7.34 Hz, 2 H) 1.10 (m, 3 H) (4H obscured by solvent signal); LC-MS 388 (M -H)"; Purity (HPLC) 100%. Legend to Scheme 7: i) nBuLJ, diofliy] efiier; ii) SO; gas; iii) beiizyIbTonmie(s), DMF, heat; iv) dkmme(s), KCOj, DMF, heat; v) HCl, diethyl etber. INTERMEDLAIE 70 L!ttiium4-chlorofliieno{3-c]pyridine-2-saU1nate 2-Bromo-4-clilorothieno[3,2-cJpyridine (5.0O g, 20.1 mmol) was suspmded in dry ether (100 ml) and the mixture was cooled to -78 °C under Ni-atmosphere. n-BuLi (1.6M in hexane, 15 mL) was added and the reaction mixture was stirred at —78 °C for 2h. SO; (g) was then bubbled threw the reaction mixture for Ih. ASer the gas bubbling iiad stopped the reaction mixture was stirred fore one more hour at -78 °C and was then, allowed to warm to room temperature. The precipitate that had formed was filtered and washed with e&er to give the sulfonate liSiiiim salt (3.59 g, 74 %) That was used in the next step without fiirther purification. 'H NMR (270 MHz, DMSO-ds) 5 ppm 7.26 (s, 1 H) 7.99 (d, .-5.54 Hz, 1 H) 8.14 (d, J=5M Hz, 1 H). MS (M-Li+1) 234. Benzylation of snlfinate salts (Mediod P) To a suspension of litiiium 4-chlorothienoj;3,2-c]pyridine-2-«ulfinate (100 mg, 0.42 mmol) in dry DMF (2 mL) was added a benzylbromide (0.83 mmol, 2 equiv.) and the tnixture heated with stirring for 16 h at 110 °C. Analysis by LCMS showed desired product and no starting material remaining. The mixture was treated with polystyrene-ophenol (200 mg) and was rolled for 16 h. The suspension was filtered washing with further DMF (2mL). This material was reacted further witiiout purification. Nncleophilic snbstitatioii of chlorine (Method Q) To a crude solutions of benzylsulfone in DMF (4 mL) are added potassium carbonate (172 mg, 1.25 mmol) and tert-butyi-pipa-azine-l-carboxylate (155 mg, 0.84 mmol). The resulting mixtures are heated for 16 h at 110 °C. LCMS shows desired compound and no starting material. The reaction mixtures are filtered and then the solvent removed under reduced pressure. The desired compounds are isolated pure follovidng preparative HPLC. BOC-deprotection (Method R) Tlie BOC N-protected piperazine derivatives are dissolved in HCl/ diethyl ether (I mL, l.OM) at room temperature and stirred for 16 h. Removal of the solvent under reduced pressure gave tiie crude hydrochloride salts. Trituration with acetonitrile gives the desired compound as a white solid. INTERMEDL\TE 71 teK-ButyI-4-[2-(ben:lsolfDDy!)thienoI352-c]pyridin-4-yI]piperazine-l-carboxyIate Lithium 4-chlorothieno[3,2-c]pyridine-2-sulfinate (0.44 mmol) was treated witii benzylbromide (0.59 mmol) as described in MeQiod P above and ttien reacted further with (ert-butyl-piperazine-l-carbox>date as described in Method Q. Yield O.009 g (7 % over two stqjs). 'HNMR(300MHZ, CDClj) 5 8.14 (d, J=5.5 Hz 1 H), 121-1M (m, 5 H), 7.15-7.21 (m, 2 H), 4.45 (s, 2 H), 3.50-3.56 (m, 4 H), 3.40-3.45 (m, 4 H>, 1.49 (s, 9 H); MS (ESI+) for C23 H27 N3 04 S2 m/z 474 (M+H)". HPLC 77%, RT 3.93 min (ACE3 C8 50x4mm, 5-50% acetonitrile in 3 min). INTERMEDIATE 72 fcrt-Bi]tyl-4-(2-{[4-(trifluoroniethyI)beiizyl]siilfGnyl}thie!io[3,2-c]pyridiii-4- yI)piperarine-l-carbosyIafe Lithium 4-chlorotiiieQo[3,2-ojpyridine-2-sulBnate (0.44 inmol) was treated with 4-(trilluoroinethyl)benzylbtomide (0.59 mmol) as described in Method P above and ihen reacted iurther with fert-birtyl-piperazine-l-carbox)date as described in Method QF. Yield 0.02 g(I6 % over two stejs). Beige solid. 'H NMR (300 MHz, CDCIs) 5 8.16 (d, J=6 Hzl H), 7.53-7.61 (d, 9 Hz 2 H), 7.49 (s, 1 H), 7.26-7.36 (m, 4 H), 4.51 (s, 2H), 3.49-3.60 (m, 4 H), 3.36-3.49 (m, 4 H), 1.49 (s. 9 H); MS (ESR) for C24 H26 F3 N3 04 S2 m/z 542 (M+H)*. HPLC 71 %, RT 4.07mi[i (ACE3 C8 50x4mm, 5-50% acetonitrile in 3 min). INTERMEDIATE 73 (ert-Biityl-4-{2-[(S-bromobenzyl)s«Ifonyl]thieno{3,2-c]pyridia-4-yI}piperazine-l- carboxylate Lithium 4-chIorofeienot3,2-c]pyridine-2-suiaiate (0.44 mmol) was treated with 3-faromobenzylbromide (0,59 mmol) as described in Method P above and then reacted finder with lert-butyl-piperazine-l-caifaoxylate as dcribed in Metiiod Q. Yield 0,023 g (10 % over two steps). Edge soli4 H NMR (300 MHz, CDCI3) 5 8.16 (d, J=6 Hz, IH), 7.50-7.55 (m, 2 H), 7.32-7.40 (m, 2 H), 7.10-7.24 (m, 3 H), 4.44 (s, 2 H), 3.61-3.73 (m, S H), 1.50 (s, 9 H); MS (ESI+) for C23 H26 Br N3 04 S2 m/2 554 (M+H)*. HPLC 77 %, RT 4.07imn (ACE3 08 50x4.6mm, 5-50% acetonihile m 3 min). INTERMEDIATE 74 terl'-BBtyI-4-(2-{[3-(trifhioromethyr)beiizyIIsalfonyl}thienoI3,2-cJpyriilin-4- yOpiperazine-1-carboxylate Lithium 4-chloroftiieno[3,2-c]pyridine-2-sulfinate (0.44 mmol) was treated with 3-(trifluorometiLyl)benzylbroniide (0.59 mmol) as described in Method P above and then reacted farther with rert-butjd-piperasane-l-carboxylate as described in Method Q. Yield 0.023 g (10 % over two steps). Beige solid. 'H NMR (300 MHz, CDClj) 5 B.14 (d, J= 6 Hz, 1 H), 7.85-7.91 (m, 1 H), 7.61-7.72 (m, 2 H), 7.50-7.60 (m, 1 H), 7.12-7.31 (m, 2 H), 4.74 (s, 2 H), 3.52-3.71 (m, 8 H), 1.50 (s, 9 H); MS (ESI+) for C24 H26 F3 N3 04 S2 m/z 542 (M+H)"". HPLC 85 %, RT 2.13iniii (YMC ODS AQ, 33x3imn, 10-90% acetonitrile in 3inin). INTERMEDIATE 75 ierButyl-4-(2-{[2,5-bis(trifliioromethyl)benzyI]sulfonyl}thienol3,2-clpyridm-4- yl)piperazine-l-carboxylate Lithium 4-clilorofliieno[3,2-c]pyridnie-2-siilfinate (0.44 mmol) was treated with 2,5-bis(triiluoromethyl)benzylbromide (0.59 mmol) as described in Method P above and then reacted further with (ert-butyl-piperazine-1-carboxyIate as described in Method Q. Yield a 01 g (4 % over two st). Beige solid. H mffi {300 MHz, CDClj) 5 8.16 (d, J= 5.8 Hzl H), 8.00 (s, 1 H), 7.74-7.85 (m, 3 H), 4.76 (s, 2 H), 3.56-3.64 (m, 4 H), 3.47-3.56 (m, 4 H), 1.49 (s, 9 H); MS (ESI+) for 025 H25 F6 N3 04 S2 m/z 610 (M-hH) HPLC 73 %, RT 2.36mm (YMC ODS AQ, 33x3rmn, 10-90 % acetonitrile in 3 min). INTERMEDIATE 76 (CT(-Botyl4-{2-[(4-methylbenzyI)sulfonyl]thieno[3clpyridin-4-yI}piperazine-l- carboxjlate Lithium 4-chlorothieno[3,2-c]pyridine-2-sulfinate (0.44 mmol) was treated with 4-meaiylbenzylbromide (0.59 mmol) as described in Method P above and then reacted forther with (ert-butyl-piperazine-1-carboxylate as described in Method Q. Yield 0.005 g (3 % over two steps). Beige soUd. 'H NMR (300 MHz, CDCI3) 5 8.15 (d, J= 6 Hz 1 H), 7.40 (s, 1 H). 7.00-7.16 (m,4H), 4.42 (s, 2H), 3.46-3.60 (m, 4H), 3.37-3.46 (m, 4H), 2.34 (s, 3 H), 1.49 (s, 9 H); MS (ESI+) for 024 H29 N3 04 S2 m/z 488 (M-hH). HPLC 69 %, RT 2.06min (YMO ODS AQ, 33x3imn, 10-90 % acetonitrile in 3 min). It is preferred that; RMS (a) Ci zikyU or (e) a group Ar; Aris (a) phenyl, (b) l-naphOiyi, (c) 2-nE5ththyl, or (f) a 5 to 7-ineinbered, optionally aromatic, partially saturated or completely saturated, heterocyclic ring containing 1 to 4 heteroatoms, selected ftom oxygen, ititrogKi and sulfur, ■whemn the group Ar is substituted in one or more positions with (a)H. (b) halogen, (c) C,.6 alkyl. (d)-CF3, ffiCwalkoxy, (g) C2 afltenyl {preferably C2 aUcKiyl), (m) straight or branched Ci-s hydroxyalkyi, (n) phenyloxy, (o) benzyloxy, (v)-NR*COR (X) -S02NR*'R (l) -S(0)X wherein n is 0.1,2 or 3; (m) -S-CCi-a) alkyl, or (ad)-SCF3; Ris (a)H,or (b)Cialkyl; or R and S} are linked to form a group -CH1CH1OCHzCHi-; XandYareH; R. is iBdepetideotily (a)H, (b) C].5 alkyl (preferably C1.3 alkyl), in particular methyl, (d)-CH2-CH2-OH,or (e)-ai2-CH2-OCH3. q=lot2, m = I or 2, 11 = 0, and R is independently (a)H, (b)Ci.3aIkyl, (d)-CH2-CH2-OH,or (e) -CH2-CH2-OCH1. R is independently (a)H, (b) C5.3 alkyl, (d) ~CH2-CH2-OH, or (e)-CH2-CH2-OCH3. It is preferred that R is H or meUiyl. It is also preferred that R is piperazine; homopiperazine; 2,6-dimetbylpiperazine; 3,5-dimethylpiperazine; 2,5-diinethylpiperazine; 2-mediylpiperazine; 3-metliylpiperazine; 2,2-dimeliiylpiperaziiie; 3,3-(iimethylpiperazine; piperidine; l,3,6-tetrahydro-pyrazin6; or 4-pyiTolidLH-3-y]oxy. It is prefered that the groups Y and X are attached to any imsubstitiited carbon atom. It is preferred that D is pjrrolyl, thienyl or furanyl. It is preferred fliat y = 0 and x = 2, Another object of flie present invention is a compound of the genera! formula (HI} It is also preferred that D is pyrrole and P is attached to fee nitrogen atom in the D ring, giving a skeleton as any of the following; wherein P is of the formula (a) or (b) as defined ia claim 1, preferably whem S? is H, X, Y, and R are as defined in claim l,and wherein D is a five-membered heteroaiyl ring, said heteroaryl ring comprising one or two atoms selected from fhe groi consisting of nitrogen, sulfiii and oxygen; and when fee heteroaryl ring comprises one or two nitrogen atoms, a group R. is attached at any nitrogoi atom which allows (he substitution. (c) benzyl, (d) -CH2-CH2-OH, or (e) CH2-CH2-O-CH3, and wherein P is of the fonniila (a) or (b) as defined in claim 1, preferably wherein R is H, X, Y, and R'are as defined in claim 1. or a phannaceaticaliy acceptable salt thereof, whereia P and R are attached to (he same ling or to different rings of rings A and B, wherein A, B, Y, P, and Rs are as defined in claim 1. Preferred compounds of fee fonniila (D) are 6-Benzenestilfonyl-4-piperaziB-l-yl-quinoline hydrochloride; 6-[(2-f1uorapheiiyl)sulfony!]-4-piperazin-i-y}qtiinoIiiiehydrtjciiJoiide; 6-{l-Nq)hlhy!siilfonyI)-4-pipsazin-l-yIqiiinoIine hydrochloride; 6-[(3,4-I>ichlorophsiyl)sulfonyl]-4-piperazm-l-ylquinoliiie hydrochloride; 6-[(3,5-DiniethylphenyI)siilfonyl]-4-pipera2in-l-ylqimioIine hydrochloride; 6-[(2-Cfiioro-6-me8iy[pitieny!)stdfbnyi]-4-piperazin-1 - jqidnoiine hydrochloride; 6-[(4-Cblorchenyl)sulfonyl3-4-piperazin-l-ylquinolinehihocliloride; 6-[(2-Meth>4-tert-butyi-phenyJ)siUfonyi]-4-piperasin-l-yiqmnoIine hydrochloride; 6-[(3,4-Dimethylphenyl)sulfonyl]-4-piperazin-l-ylquinoline hydrochloride; 6-[(2,3-DiCH1orophenj1)sut&nyi]-4-piperaziQ-i-yIquinoIine hydrochloride; 6-[(4-tert-Butylphenyl)sulfonyl]-4-piperazin-l-ylqtmiohne hydrochloride; 6-[(4-Isopropyhenyl)su!fonyl]-4-piperazin- i -ylquinohne hydrochloride; (4-Piperazin-l-yl-6-{[4-(trifluororaethyl)phenyl]sulfojiyl}qiiinoIine hydrochloride; 6-[(4-tert-Butyipheayl)snlfDnyi]-4-(I,4-diazepan-I-yi)qiiinoIinehydrochloride; and 4-(l,4-Diazepan-l-yI)-6-[(4-isopropyiphenyl)sulfonyi]qiiinoline hydrochloride. Preferred compounito of the formula (IH) are 7-{2-ChIoro-6-methyI-ben2enesuIfonyI)-l-piperazin-I-yl-isoquinohne hydrochloride; 7-(2-Butyl-benzenesiilfonyl)-l-pipera2in-l-yl-isoquinoline hydrochloride; 7-(3,4-DichIoro-benzenesulfonyl)-l-piperaziD-l-yl-isoquiQoIine hydrochloride; 7-{2,4-Dimethyi-benzenesulfonyl)-l-piperazin-l-y]-isoqiiinoline hydrochloride; 7-(2,5-Dimethyl-baizCTesulfonyl)-l-pipera2in-l-yl-isoquinoline hydrochloride; 7-(p-Chloro-benzenesulfonyl)-3-piperazin-]-yl-isoquinoline hydrochloride; 7-Benzenesul&nyi-l -[1,4]diazepan-l-yl-isoquiiioiine,hydrochloride; 7-(4-tert-Butyl-benzenesulfoiiyI)-l-[l,4]dia2epan-I-y!]-isoqumQHne, hydrochloride; 7-(2-Ch]oro-6-inethyl-ben2enesulfonyI)-l-[l,4]diazepan-l-yl]-isoqii!no!ine hydrochloride; 7-(3,5-DimethyI-benzenesiilfonyl)-l-[l,4]diazepan-l-yl]-isoqidnoline hydrochloride; 4-(4-Meihy]-piper2zin-J -y])-thieiK'[3,2-c]pyridme-2-suIfonic acid phsnylamide hydrochloride; 5-ChIoro-N-[4-(piperidin-4-yloxy)-l-nhthyl]lhiophene-2-stUfonamidehydrochioride; 4-CMoTO-N-{4-[(3S>pymilidiD-3-yloxy]-l-nhliyl}benzenesiiIfonaimde hydrochloride; and 4-Chloro-N-{4-[(3R)-pyiTohdm-3-yloxy]-l-naphthyl}be!izeDesiilfonamide hydrochloride. Another object of "Hie present invention is a process for the preparation of a compound above, said me&od comprising the steps of; (a) Mitsonobu reaction of 4-nitro-l-iiaphtiiol with boc-protected 3-hydroxypyrrolidine or 4-hydroxypiperidine; (b) reduction of the nitro group in the nitronaphlhalene obtained in step (a) to form an aminouaphthalene derivative; and (c) syndesis of a sulfonamide by reacting the aminonaphthalene obtained in step (b) with a suitable sulfonyl chloride. ' Another object of the present invention is a process for the preparation of a compound carboxylic moiety to amine by Cuitiua rearrangement; reaction of the amine group witti a sulphonylcbloride. alkylammes, benzathine, and amino acids, such as, e.g. arginine and lysins. The tenn addition salt as used herein also comprises solvates which the compounds and salts thereof are able to foim, such as, for example, hydrates, alcoholates and the like. For clinical use, the compounds of the invention are formulated into phaimaceutical foraiulations for oral, rectal, parenteral or other mode of adnunistration. Pharmaceutical formulations are usoaily prepared by mbdag tiie active substance, or a pharmaceutically acceptable salt tha'cof, witii conventional pharmaceutical excipients. The formulations can be further prepared by knovm mefliods such as granulation, compression, microencisulation, spray coating, etc. The formulations may be prepared by conventional methods in the dosage form of tablets, capsules, granule, powders, syrups, suspensions, suppositories or inj ections. Liquid formulations may be prepared by dissolving or suspending the active substance in water or other suitable vehicles. Tablets and granules maybe coated in a conventional maimer. Another object of the present invention is a compound above for use in therapy. Anotiier object of the presKit invention is a compound above, and for the case when rings A and B are both phenyl, P is any one of fomiula (a) or (c) substituted in position 7 on tiie naphthalene ring, and R is substituted in position 1 on the naphthalene ring, for use in the treatment or prophylaxis of a 5-HT$ receptor related disorder, such 3S obesity, type H diabetes, and/or disorders of the central nervous system, to achieve reduction of body weight and of body weight gain. Another object of the present invention is a compound above for use in the treatmait or prophylaxis of disorders of the cential nervous system. Another obj ect of the present invention is a compound above, for the case when rings A and B are both phenyl, P is any one of formula (a) or (c) substituted in position 7 on the naphtiialene ring, and R' is substituted in position 1 on ihs naphthalene rir, and for the case when ring D is a pyrrole ring, P is of the formula (c) and R is of the formula Malonic acid (44.40 g, 426.7 mmol) was added to a mixture of 5-bromotbiophene-2-carbaldehyde (50 g, 261.7 mmol), piperidine (2.84 mL) and pyridine (150 mL). The mixture was refluxed for I h at 80°C and than at 100 °C over night The volariles were evaporated and the residue was dissolved in water and acidified with hydrochloric acid (pH 2). The crude product was crystallized in ethanol. Yield: 55.24 g (90.5 %). lH NMR (270 MHz, CH3OH-d4) 8 ppm 6.14 (d, >15.83 Hz, 1 H) 7.11-7.16 (m, 2 H) 7.68 (d, .7=16.36 Hz, 1 H); MS 233.1 (M-H)+; Purity(HPLC) 94 %. INTERMEDIATE 48 (2£)-3-(5-Bromofliieii-2-yl) acryloyl azide Thiortyl chloride (1,04 mL) was added to a solution of (2E)-3-(5-bromothien-2-yl) acrylic acid (1.04 g, 4.46 mmol) in chloroform (20 mL) and the mixture was refluxed for 2h at 75°C and than used in the next step. The above solution was added drop wise to a stirred suspension of sodium azide (0.58 g, 8.93 mmol), dioxane (3 mL) and water (3 mL) in an ice bath. After 10 min a precipitate appeared which was filtered off and washed with water. The residue was dissolved in dichloromethane, dried with MgSCU, filtered and the solvent was removed to afford: 0.96 g (83.4 %). lH NMR (270 MHz CH3OH-cU) 8 ppm 6.20 (d, ,7=15.57Hz, 1 H) 7.15-7.25 (m, 2 H)7.80 (d, .7=15.57Hz, 1 H); MS 258.1 (M-H)+; Purity (HPLC) 65 %. INTERMEDIATE 49 2-BromothieDO [3,2-c] pyridin-4 (5H)-oae A solution of (2£)-3-(5-bromothien-2-yl) acryloyl azide (18.00 g, 69.7 mmol) solved in dichloromethane (100 mL) was added dropwise to diphenyl ether (90 mL) at 150 °C. The temperature was increased to 220°C for lh. The mixture was cooled to room temperature followed by the addition of ether. The solid precipitated and was separated by filtration. Yield: 13.58 g (84.6 %). 'H NMR (270 MHz, DMSO-d6) 5 ppm 6.82 (d, >7.13 Hz, 1 H) 7.27 (d, >6.86 Hz, 1 H) 7.54 (s, 1 H) 11.55 (s, 1 H); MS 230.1 (M -Hf; Purity (HPLC) 92 %. INTERMEDIATE 50 2-Bromo-4-chloro-thieno [3,2-c] pyridine Phosphorus oxychlorids (4.08 g, 26.6 mmol) was added dropwise to 2-hromothieno [3,2-c] pyridin-4 (5fl)-one (2.04 g, 8.87 mmol) at 0 °C. The mixture was heated at 135 °C foi 2.5h, then carefully poured over ice water. The precipitated was collected by filtration and dried to yield 1.78 g (80.7 %) of title product. lH NMR (270 MHz, CHjOH-di) 5 ppm 7.67 (d, 1H) 7.88 (dddd, J=6,33 Hz, 2 H) 8.19 (d, /=5.54 Hz, I H); MS 248.0 (M- H)+; Purity (HPLC) 100 %. INTERMEDIATE 51 and INTERMEDIATE 52 4-ChIorotnieno [3,2-c] pyridine-2-snlfonyl chloride and 2-bromo-4-chIorothieno [3,2- c] pyridhie-3-suIfonyl chloride n-Butyl lithium (1.5 mL, 2.4 mmol) was added to 2-bromo-4-chIorouiieno [3,2-c] pyridine (0.5 g, 2 mmol) dissolved in dry THF (15 ml) at -78°C under nitrogen. The mixture was stirred for 40 inin. The above solution was added to a dry ether saturated with S02 (gas) at -78°C. The mixture was wanned to room temperature, followed by the addition of ether. The precipitate was separated by filtration. The two title products were obtained and taken to the next step wimout further purification as follows: N-cHorosuccinimide (2.07 g, 10.3 mmol) was added to [(4-chlorothieno [3,2-c] pyridin-2-yi) sulfonyl] lithium and [(2-bromo-4-chlorothieno [3,2-c] pyridin-3-yl) sulfonyl] lithium in dichloromethane (150 roL) at 0 "C. The mixture was heated at 60 °C for 2b, extracted with water (3 x 50 mL). The organic phase was separated, dried with MgSCU, filtrated and the volatiles were eliminated by vacuum distillation. The crude products were used in Ihe next step without further purification, INTERMEDIATE 53 and INTERMEDIATE 54 4-ChIoro~2-thieno [3,2-c] pyridine-2- sulfonic acid p-tolylamide and 2-bromo-4- chloro-thieno[3,2-c]pyridine-3-sulfonic acid p-tolylamide p-Toludine (30 mg, 2.87 mmol) was added to a solution of 4-chlorothieno [3,2-c] pyridine-2-sulfonyl chloride and 2-bromo-4-chloroniieno [3,2-c] pyridine-3-sulfonyl chloride (0.07 g, 0.26 mmol) in dichloromethane and pyridine (0.19 mL). The reaction was stirred at room temperature for 2h. The solvent was removed and the crude mixture was taken to the next step without further purification. purity material, the products were purified by silica gel flash chromatography. The products are used in the next step (Procedure B). Coupling with aromatic amines (Method I) To the reaction mixtures from the Method H, dissolved in DMSO (2mL), amines (15 eqw.) and K2CO3 {1 equiv.) are added. The reactions are stirred at 1006C for 24 and than concentrated. The products are purified by LC-MS. The solvents are removed under vacuum by SpeedVac and purified by preparative LCMS. The products that were not pure enough (Purity &Q%) were purified by preparative chromatography using acetonitrile-water gradients conlaining 0.1% trifiouroacetic acid. After HPLC analysis fractions fliat were > 90% pure were collected and concentrated. Deprotection of the amine in the piperazine -was performed by first dissolving the substance in methanol and adding portions of 1M HCl/ether. The reactions are analyzed by TLC- The solvents were concentrated under vacuum by a SpeedVac. Deprotection of BOC-gronp (Method L) The sulfone or sulfonamide derivative (prepared by Methods H and I) were dissolved in a small amount of MeOH/DCM 1:1 and treated with an excess of 1 M HC1 in diethyl ether. Stirring at ambient temperature overnight resulted in a precipitate which were collected by filtration to give the products as their corresponding hydrochloride salts. EXAMPLE 43 4-(4-MethylpiperaziD~l-yl>N-pbenylthienoE3,2-c]pyridine-2-sii]fonamide hydrochloride The synthesis was preformed essentially as described in Method H-L. Yield: S.l mg (33.8 %). 'HNMR(270 MHz, CH3OH-d4) 5ppm 8.13 (d,.7=5.81 Hz, 1 H) 7.67 (s, I H) 7.54 (d, >=5.81 Hz, 1 H) 7.55-7.53 (m, 5H) 2.97 (s, 3 H) (4H obscured by solvent signal); LC-MS 389 (M - H)+; Purity (HPLC) 100 %. EXAMPLE 44 4-Piperazin-l-yl-thieno[3,2-c]pyridine-2-soU?onicacid(3-iluoro-5-trifluoroiriethyl-phenyl)-amide hydrochloride EXAMPLE 47 4-Piperazin-I-yl-thieno[3,2-c]pyridine-2-sulfonic addp-tolylamide hydrochloride To a solution of 4-ohloro-thieno[3J2-c]pyridine-2-si!lfonyl chloride (0.640 g, 2.39 mraol) in DCM (20 mL) was added pyridine (1.9 mL, 23.9 mmol) followed byj?-tolylamine (0.307 g, 2.86 mmol). The reaction mixture was stirred at room temperature for 16 hours. The mixture was concentrated and re-dissolved in DMSO (10 mL), piperazine- 1-carboxylic acid tert-bvtyl ester (1.34 g, 7.17 mmol) andK2C03 (0.989 g, 7.17 mmol) were added. The mixture was stirred at 100 eC for 16 hours and then concentrated. The crude reaction EXAMPLE 50 4-(4-Methylpiperazra-l-yI)-JV- (2-thien-2-ylethyI) thieno [3,2-c] pyridine-2- solfonamide hydrochloride EXAMPLE 53 N~ (3-ChIorobeiizy0-4-(4-inethylpipera2$ii-l-yl) thieno [3,2-c] pyridine-2-snlfonaniide hydrochloride EXAMPLE 56 4-(4-Meftylpiperaztn-l-yI)-iV- (4-chIoro-2, 5-dimethoxyphenyl) thieno [3,2-c] pyridioe-2-snIfonaniide hydrochloride EXAMPLE 63 4-Piperazin-l-yI-N-[-3-(trifluoromethyI)pheiiyl}tliieno[3^-c]pyridiite-2-snlfonamide hydrochloride The synthesis was preformed essentially as described in Method H-L. Yield: 2.6 mg (1.2 %). !H NMR (270 MHz, CH3OH-d4) 5 ppm 8.05 (d, .7=6.60 Hz, 2 H) 7.81-7.60 (m, 3H) 7.50-7.47 (m, 2H) 3.94-3.90 (m, 4H) 3.56-3.49 (m, 4H); LC-MS 443 (M - H)+; Purity (HPLC) 99 %. EXAMPLE 64 N-(3-EthylphenyI)-4-piperazin-l-ylthieno[3,2-c]pjTidine-2~salfonamide hydrochloride The synthesis was preformed essentially as described in Method H-L. Yield: 1,4 mg (0.7 %). *H NMR (270 MHz, CHsOH-d,) 5 ppm 8.35 (s, 1H) 7.58-6.92 (m, 7H) 3.54-3.44 (m, 2H) 3.01-2.95 (m, 4H) 2.66 (s, 1H) 2.18-2.01 (m, 3H)); LC-MS 403 (M - H)+; Purity (HPLC) 100 %. EXAMPLE 65 N-(3,4^DimethoxypheDyi)-4-piperazui-l-ylthleno[3,2-cIpyridiiie-2-siilfonaniide hydrochloride The synthesis was preformed essentially as described in Method H-L. Yield: 7.7 mg (3.6 %). !H NMR (270 MHz, CH3OH-&,) 3 ppm S.04 (d,7=6.60 Hz, 1 H) 7.77-7.75 /m, 2H) 6.85-6.83 (m,2H) 6.68-6.83 (m, 1H) 3.87-3.8S (m, 4H) 3.77-3.75 (m, 6H) 3.49-3.45 (m, 4H) 2.65 (s, 1H); LC-MS 435 (M - H)+; Purity (HPLQ 98 %. EXAMPLE 66 N-(VBromo-2-melhylphenyl)-4^pip^razm-l-ylthienoP,2-c\pyriduie-2-s\ilionanude hydrochloride The synthesis was preformed essentially as described in Method H-L. Yield: 12.2 mg (5.3 %). 'H NMR (270 MHz, CH3OH-d,) S ppm 8.07 (d, >6\33 Hz, 1 H) 7.86-7.79 (m, 2H) 7.40 (d, J=l,58 Hz, 1H) 7.30-7.29 (m, 1H) 7.DS (d, J=8.71 Hz, 1H) 3.96-3.92 (m, 4H) 3.53-3.51 (4H) 2.66 (s, 1H) 2.11 (s, 3H); LC-MS 467 (M - H)+; Purity (HPLC) 90 %. EXAMPLE 67 2-(4-KperaziB-l-y!-thieno[3,2H:]pyridiiie-2-snIfonyl)-l,2,3,4-tetra]iy€Lro-isoqumoline hydrochloride The synthesis was preformed essentially as described in MethodH-L frora4-[2-(3,4- dihydro-lH-isc acid ierf-butyl ester (0.235 mmol, 1 equiv.). Yield: 4.0 mg. LC/MS: tR= 0.801 (System: 30 % to 60 % ACN in 1.5 mm, Hypersil BDS), Purity: 92%. MS: 415 (M+l) 1H NMR (270 MHz, DMSO-ds)Sppm2.87 (t,7=5.81 Hz, 2 H) 3.30 (s, 4H)4.43 (s,2 H) 7.15 (m, 4 H} 7.70 (d, 7=5.54 Hz, 1 H) 8.12 (s, 1 H) 8.18 (d, 7=5.54 Hz, 1 H) 6 aliphatic protons were obscured by the water-peak in the spectra and so could not be analyzed. EXAMPLE 68 4-Piperazra-l-yl-thieno[3^-cIpyridiBe-2-snifonicacid(2-thiopiien-2-yl-ethyI)-amide hydrochloride The synthesis was preformed essentially as described in Method H-L from 4-[2-(2- tmophen-2-y]-ethylsmfamoyl>thieiio[3,2-c]pyrid^ butylester (0.235 mmol, 1 equiv.). Yield: 8.7 mg. LC/MS: tR= 0.430 (System: 30 % to 60 % ACN in 1.5 min, Hypersil BDS), Purity. 93 %. MS: 409 (M+l) *H NMR(270 MHz, DMSO-ds) Sppm2.25 (s, 1 H) 2.75 (s, 1 H) 2.96 (t,7=6.99 Hz, 1 H) 3.16 (q,7=6.51 Hz, 1 H)3.31 (s, 4H)3.70 (s,4H) 6.90 (m, 1 H) 7.32 (t,7=5.54Hz, 1 H) 7.70 (d,7=5.81 Hz, 1 H) 8.04 (d, >1.85 Hz, 1H) 8.18 (d,>5.54Hz, 1H) 8.36 (m, 1 H) 9.05 (s, 1 H). EXAMPLE 69 4-Piperazin-l-yl-tliieno[3,2-c]pyridine-2-siiIfoiiicacid(4-chloro-2,5-diniethoxy-j>henyl)-armde hydrochloride The synthesis was preformed essentially as described in Method H-L from 4-[2-(4-chloro-2,5-dimetho}Q'-phenylsul&moyl)-tMeQo[3^-c]pyridk-4-yI]-piperazme-l-carboxyIicacid m-t-butyl ester (0.112 mmoL 1 equiv.) was used as the thienopyricHne in Method C. Yield: 14,7 mg. LC/MS: tR= 0.610 (System: 30 % to 60 % ACN in 1.5 min, YMC), Purity: 92 %. MS: 469 (M-H) lH NMR (270 MHz, DMSO- dg) 8 ppm 3.17 (s, 1 H) 3.27 (s, 4 H) 3.38 (s, 3 H) 3.58 (d,^=4.22Hz, 4H) 3.77(s, 3 H) 7.0S (s, 1H) 7.69 (d, .7=5.81 Hz, 1 H) 7.81 (s, 1 H) 8.16 (d, >5.8l Hz, 1 H) 9.07 (s, 1 H) 10.17 (s, 1 H). EXAMPLE 70 4-Piperazi]i-l-yI-thie!io[3^-c]pyri{iiiie-2-si]!fonic acid phenethyl-amide hydrochloride The synthesis was preformed essentially as described in Method H-L from 4-(2-phenethylsulianioyl-tbiaio[3,2-c]pyridin-4-yl)-piperazine-l-carboxylic acid tert-butyl ester (0.112 mo], 1 equiv.). Yield: 3.8 rag. LC/MS: tE= 0.410 {System: 30% to 60% ACN in 1.5 min, YMC), Purity: 91 %. MS: 403 (M+l) lH NMR (270 MHz, CH3OH-d4) 5 ppm 1.44 (d, >7.13 Hz, 2 H) 3.51 (d, .7=4.75 Hz, 4 H) 3.54 (s, 2 H) 3.94 (m, 4 H) 7.05 (m, 4 H) 7.16 (m, 1 H) 7.62 (s, 1 H) 7.72 (d, .7=6.60 Hz, 1 H) 8.00 (d, .7=6.60 Hz, 1 H). EXAMPLE 71 4-PiperaziD-l-yl-thieno[3^-c]pyridine-2-sulfoiiic acid (2,6-diethyl-pheiiyl)-ainide hydrochloride The synthesis was preformed essentially as described in Method H-L from 4-[2-(2,6-dethyl-pheiiyIsulfamoyi)-thieno[3,2-c]pyrid4n^yl]-piperazine-l-carboxyIic acid fert-butyl ester (0.112 mmol, 1 equiv.). Yield: 9.0 mg. LC/MS: tR= 0.830 (System: 30 % to 60 % ACN in 1.5 min, YMC), Purity: 92 %. MS: 431 (M+l) !H NMR(270 MHz, DMSO-D6) S ppm 0.96 (t, .7=7.52 Hz, 6 H) 2.25 (m, 1 H) 2.43 (s, 2 H) 2.75 (t, 7=1 .72 Hz, 1 H) 3.26 (s, 4 H) 3.62 (s, 4 H) 7.09 (s, 1 H) 7.12 (s, 1H) 7.23 (m, 1 H) 7.73 (d, >5.81 Hz, 1 H) 7.77 (s, 1 H) 8.19 (d, .7=5.81 Hz, 1 H) 9.04 (s, 1 H) 9.95 (s, 1H). EXAMPLE 72 4-Piperazin-l-yl-thieno[3,2-c3pyridine-2-sulfoiiic acid (3-phenyl-propyl)-amide hydrochloride The synthesis was preformed essentially as described in Method H-L from 4-[2-(3-phenyl-propylsulfamoyl)-mieno[3,2-c]pyridni-4-yl]-piperazrne-l-carboxylic acid tert-butyl ester (0,112 mmol, 1 equiv.). Yield: 13.0 mg. LC/MS: tK= 0.726 (System: 30 % to 60 % ACN in 1.5 min, YMC), Purity: 91 %. MS: 417 (M+l) 'H NMR (270 MHz, CHsOH-d*) 5 ppm 1.82 (m, 2 H) 2.63 (m, 2 H) 3.04 (t, .7=6.86 Hz, 2 H) 3.55 (s, 4 H) 4.09 (s, 4 H) 7.16 (m, 4 H) 7.82 (d, .7=6.60 Hz, 1 H) 8.05 (d, .7=6.33 Hz, 1 H) 8.14 (s, 1 H). EXAMPLE 73 4-Piperazm-l-yl-thieno[3^-c]pyridiBe-2-siilfonic acid (3,3-diphenyI-propyI)-aiiiide hydrochloric add The synthesis was prefbnned essentially as described in Method H-L from 4-[2-(3,3- diphenyl-propylsmf^oyl)4mem[3,2-c]pyridm-4-yT^^ acid tert- butyl ester (0.112 mmoL 1 equiv.). Yield: 14.4 mg. LC/MS: te= 1.109 (System: 30 % to 60 % ACN in 1.5 min, YMC), Purity: 93 %. MS: 493 (M+l) JH NMR (270 MHz, DMSO-ds) 5 ppm 2.20 (m, 2 H) 2.80 (m, 2 H) 3.29 (s, 4 H) 3.67 (d, J=5.0l Hz, 4 H) 4.01 (m, 1H) 7.14 (m, 8 H) 7.71 (d, J=5.81 Hz, 1 H) 7.95 (s, 1 H) 8.18 (d, ^=5.81 Hz, 1 H) 8.27 (m, 2 H) 9.13 (s, 2 H). EXAMPLE 74 4-Piperazin-l-yI-tiiieno[3^-c]pyridine-2-snlfonic add p-(5-inethoxy-lH-indol-3-yI)- ethyl]-amide hydrochloride The synthesis was preformed essentially as described in Method H-L from 4- {2-[2-(5-meltoxy-lH-irdol-3-yl)-emylsulfimoyl]-thieao[3,2^]pyridin-4-yl} -piperazine-1 -carboxylic acid tert-butyl ester (0.112 mmol, 1 equiv.). Yield: 6.1 mg. LC/MS: tR= 0.364 (System: 30 % to 60 % ACN in 1.5 min, YMC), Purity: 91 %. MS: 472 (M+l) *H NMR (270 MHz, CH3OH-d4) 5 ppm 2.85 (t, ^6.20 Hz, 2 H) 3.48 (t, ^=6.20 Hz, 2 H) 3.55 (m, 4 H) 3.80 (s, 3 H) 4.02 (m, 4 H) 6.44 (dd, .^8.71,2.37 Hz, 1 H) 6.80 (m, 2 H) 6.97 (s, 1 H) 7.64 (s, 1 H) 7.67 (s, 1 H) 7.97 (c. >6.60 Hz, 1 H). EXAMPLE 75 4-Piperazin-l-yl-thieno[3^-c]pyridine-2-SBlfoiiic acid 4-triflHoromethyl-beiizylamide hydrochloride The synthesis was preformed essentially as described in Method H-L from 4-[2-(4- lrifluorometflyl-beaizylsnlfair^ (ert-butyl ester (0.112 mmol, 1 equiv.) was used as the thienopyridine in Method C. Yield: 1.9 mg. LC/MS: tR= 0.771 (System: 30% to 60% ACN in 1.5 min, YMC), Purity: 91%. MS: 457 (M+l) *H NMR (270 MHz, CHaOH-dj) 5 ppm 3.54 (m, 4 H) 3.98 (m, 4 H) 4.36 (s, 2 H) 7.49 (m, 4 H) 7.74 (d, >6.86 Hz, 1 H) 8.02 (s, 1 H) 8.07 (d, >6.60 Hz, 1 H). EXAMPLE 76 4-Piperazto-l-yI-thieno[3^Ipyridine-2-siitfoiiic acid benzyl-etbyl-sniide hydrochloride "Hie synthesis was preformed essentially as described in Method H-L from 4-[2-(benzyl-ethyI-sulfemoyl)-thieao[3^1pyridin^yl]-pipeTazme-l-caiboxj4ic acid tert-butyl ester (0.112 mmol, 1 equiv.). Yield: 6.4 mg. LC/MS: tR= 0.930 (System: 30 % to 60 % ACN in 1.5 min, YMC), Polity: 95 %. MS: 417 (M+l) lH NMR (270 MHz, CHjOH-d,) 8 ppm 1.03 (t, >7.13 Hz, 3 H) 3.37 (m, 2H) 3.57 (s, 2H) 3.75 (m, 2 H) 4.11 (s, 2H) 4.50 ($, 2 H) 5.80 (s, 1 H) 7.32 (m, 5 H) 7.84 (d, .£=6.60 Hz, 1 H) 8.07 (d, .£=6.60 Hz, 1 H) 8.14 (s, 1 H). INTERMEDIATE 55 (!^-BotyI-4-(MK3^thyIphenyI)ammo]sttlfoHyi}^eno[3^c]pyridia-4-y!)piperazui6- l-carboiylate Prepared from tert-batyi 4-[3^cMorosulfcmyI)thieno[3^-c]pyridin-4-yl]piperazine-l-carboxylate (90.0 mg, 0J215 mmol) and 3-ethylanffine (33.9 mg, 0.28 mmol) to give the title compound as an ofpwbite solid (82.7 mg, 76 %). lH NMR (400 MHz, CDCU) 5 1.03 (t, J - 7.5 Hz, 3 H),1.4S (s, 9 H), 2.47 (q, J= 7.7 Hz, 2 H), 3,00-3.53 (m, 6 H)s 4.02-4.44 (in, 2 H), 6.66 (d, J= 8.0 Hz, 1 H), 6.75 (s, 1 H), 6.66 (d, I« 8.0 Hz, 1 H), 7.02 (t, J= 7.8 Hz, 1 H), 7.67 (d, J = 5.5 Hz, 1 H), 8.24 (s, 1 H), 8.39 (d, J = 5.5 Hz, 1 H), 9.80 (s, 1 H). MS (ESH-)m/z 503:2 (M+H)+. HPLC 97 %, RT: 3.93 mm (5-99 %MeCN over 3 mm). EXAMPLE 77 N-(3-EtbylpbenyI)-4^iperaM-l-ylthJeaoI3^^]pyriduie-3-snlfoiiaiiiide hydrochloride Prepared from tert-butyl 4^3-{[(3-eti3ylphenyi)ainmo]sulfonyI}tiiieno[3!2H:]pyridin-4-yI)piperazine-l-carboxyIate(81.1 mg, 0.161 n^rol) which afforded 19 mg (98 %) of the product as a white solid (38.0 mg, 54 %). 'H NMR (400 MHz, CH3OH-di) 8 1.09 (t, /*= 7.5 Hz, 3 H), 2.51 (q, /= 7.5 Hz, 2 H), 3.59 (br.s, 8 H), 6.89-6.92 (m, 3 H), 7.12-7.14 (m, 1H), 8.06 (d, /= 6.0 Hz, 1 H), 8.36 (d, /= 6.0 Hz, 1 H), 8.49 (s, 1 H). MS (ESI+) m/z 403.2 (M+H)+. HPLC 95%, RT: 3.02 min (5-99% MeCN over3 min). INTERMEDIATE 56 tert-Bnfyl^S-bromothienofS^-cIpjTidiH-^-yrjpiperazine-l-carboxylate A mixture of 3-bromo-4-chIarothieno[3^-c]pyridine (729 mg, 2.93 mmol), tert-butyi piperaztne-l-carboxylate (1.64 g, 8.80 mmol) and K2CO3 (811 mg, 5.87 mmol) in DMSO (45 mL) was stirred for 5 days at 100 °C. After addition of H20 and ethyl acetate, the layers were separated. The water pliase "was extracted twice wim ethyl acetate, and the combined organic phases were washed with water and brine and dried (MgSCM). After filtration and removal of the solvent, the residue was purified by silica gel flash chromatography (pentane/ethyl acetate, 8:2) to give the product as a white powder (398 mg, 34 %). HPLC 99%, RT: 3.27 min (5-99% MeCN over 3 minJ.'H NMR (400 MHz, CH3OH-U4) 5 1.48 (s, 9 H), 3.21 (br.s, 4 H), 3.71 (s br., 4 H), 7.61 (d, /= 6.1 Hz, 1 H), 7.72 (s, 1 H), 8.08 (d, J= 5.6Hz, 1 H). MS (BSI+) m/z 398.2 (M+H)+. INTERMEDIATE 57 {4-[4-(&rt-Biitoiycari)onyI)prperazin-l-yI]thienoE3^]pyridm-3-yl}siilfonyOIithinm To a suspension of rert-Butyl 4^3-bromotMeno[3,2-c]pyridm-4-yI)piperazine-l-carboxylate (4.055 g, 10.18 mmol) in diethyl ether (30 mL) at -78 °C under N2 atmosphere was added dropwise an 1.6 M solution of n-BuLi in hexanes (9.5 mL, 15.2 mmol). After 1 h of stirring, a saturated solution of SO2 in THF (25 mL) at-78 °C was transferred via a cannula to the mixture. The reaction was allowed to gradually increase to ambient temperature over night. The solvent was evaporated, and the residue was washed with several portions of diethyl ether and then dried under vacuum to give 4.094 g of an off-white solid consisting of 66 % of the title compound and 34 % of (n-burylsulfonyl)utnrum as by-product This rnixture was used without any further purification in the next step. *H NMR (400 MHz, CH3OH-di) 6 1.48 (s, 9 H), 3.22 (br.s, 4 H), 3.72 (s br., 4 H), 7.60 (d, J= 5.5 Hz, 1 H), 8.06 (d, J= 5.5 Hz, 1 H), 8.14 (s, 1 H). MS (ESI+) m/z 3S4.0 (M+H)4". HPLC RT: 2.62 min (5-99% MeCN over 3 rain). INTERMEDIATE 58 (^-Butyl^[3-({^orosnlfony^tlueaio[3^-c]pjTi(Im-4-yripiperazine-l-carboiylate To a suspension of ({4-[4^rert-biitoxycariKmyI^iperazm-l-)d]oueiw[3^Ipyridiii-3-yl}sulfbnyl)hthium (2.751 g, 7.06 mmol (3.126 g of the crude product mixture)) in DCM (40 mL) atO °C was added N^hlorosuccrrmnide (1.338 g, 10.0 mmol). After20 minutes, the temperature was raised to ambient, and the reaction mixture was stirred for an additional 2.5 h. The resulting product solution was washed with water, and the water phase was extracted with DCM. The combined organic extracts were washed with brine and dried over MgSCv After filtration and evaporation of the solvent, the residue was washed with several portions of pentane to yield fee product as an off-white solid (2.024 g, 69 %). ]HNMR(400MHz, CHsOH-d*) 8 1.47 (s, 9 H), 3.11 (br.s, 4H), 3.2-4.3 (sbr., 4 H), 7.68 (d, /= 5.5 Hz, 1 H), 8.45 (d, J= 5.5 Hz, 1 H), 8.60 (s, 1 H). MS (ESI+) mlz 418.2 (M+H)+. HPLC 92%, RT: 3.76 min (5-99% MeCN over 3 min). INTERMEDIATE 59 tert-Biityl-4^3-{[(4-isopropyiphenyl)amino]siiKonyl}tMeno[3^-c]pyridin-4- yI)pip€razme-l-carboryIate Prepared from terf-btttyl 4-[3-(cbJorosiilfonyI)tm'eno[3^<: carboxylate mg mmol and to give the title compound as an off-white solid nmr mhz cdc13 hz h j="6.9" ms mjz hplc rt: min mecn over> EXAMPLE 78 N^4-ZsopropyIphenyIH^qierazm-l-yrmieoo[3^H:]pyrid%e-3-srUfoQaiiude hydrochloride Prepared from terf-butyl 4^3-{[(4-isopropylphenyI)arnmo]sm\fenyl}tm^o[3^-c]pyridin-4-yl)piperazme-1-carboxylate (60.0 mg, 0.116 mmol) which afforded 19 mg (98 %) of the product as a white solid (25.8 rag, 49.%) according to Method H-L. !H NMR (400 MHz, CH3OH-d4) 5 1.16 (d, J= 7.0 Hz, 6 H), 2.81 (sept., /= 6.8 Hz, 1 H), 3.59 (s, br., 8 H), 7.00 ■ (d, J= 8.0 Hz, 2 H), 7.10 (d, /■* 8.0 Hz, 2 H), 8.07 (s, br., 1 H), 8.37 (s, br., 1 H), 8.50 (s, 1 H). MS (ESI+) m£ 417.2 (M+H)+. HPLC 94%, RT: 3.14 min (5-99% MeCN over 3 min). EXAMPLE 79 N-{4-Metiiyipfeeflyl)-4^pyrr0tiofr-3-yto hydrochloride 4-Chloro-^4-methylphenyO£bimo[3^-c]pyridine-2-salfenamide (60.0 nig, 0.17 mmol) in dry DMF (1 mL) and NaH (5,1 tag, 0.21 mmol) was added to pyrrolidin-3-ol (18.5 mg, 0.21 tnmol) under nitrogen. Thfc mixture was heated in the microwave at 200°C in 5 min. The product was purified by preparative HPLC. Yield: 29.9 mg (43.4 %). JH NMR (270 MHz, CHsOH-d,) 6 ppm 8.09 (s, 1H) 7.71 (d, ^6.93 Hz, 1 H) 7.46 (d, .^6.93 Hz, 1 H) 7.47-7.44 (m, 4H) 4.67 (d, ^=3.22 Hz, 1 H) 3.97 (s, 2 H) 2.26 (s, 3H). LC-MS 390 (M -H)+; Purity (HPLC) 99%. EXAMPLE 80 N-(4-MethylphenyI)-4KpiperidiB-4-y]oJ^)tMeno|3^ hydrochloride The synthesis was preformed essaifially as described for compound of N-(4- memylplienylM^yiroBdm-3-yloxy)Mero Yield: 16.2 mg (22.7 %). *H NUR (270 MHz, CH3OH-d() 5 ppm 7.81-7.78 (m, 2H) 7.62 (d, .7=6.93 Hz, 1H) 7.13-7.04 (m, 4H) 4.05-3.94 (m, 1H) 3.90-3.88 (m, 2H) 3.63-3.58 (m, 2H), 2.27 (s, 3H)2.06-2.03 (m,2H) 2.01-1.71 (m, 2H); LC-MS 404 (M - H)+;Purity (HPLC) 99 %. EXAMPLE 81 N-(2^-Diflaort}benzyI)-4-piperazbt-l-yltlue^ hydrochloride Yield: 74.4 mg (39.2 %). !H NMR (270 MHz, CHjOH-fL;) 5 ppm 8.10-8.03 (m, 2H) 7.81 (d, J=6.68 Hz, 1H) 7.16-7.05 (m, 3H) 437 (s, 2 H) 4.11-4.07 (m, 4H) 3.59-3.53 (m, 4H); LC-MS 425 CM - H)+; Purity (HPLC) 90 %. EXAMPLE 82 N-(3-BoE3^-cJpyridine-2-siUfonamide hydrochloride Yield: 74.4 mg (44.7 %). !H NMR (270 MHz, CH3OH-cU) 8 ppm 8.04-8.01 7.85 (d, ,£=6.93 Hz, 1 H) 7.22-7.15 (m, 4H) 4.30 (s, 2 H) 4.144.10 (m, 4H) 3.60-3.54 (m, 4H); LC-MS 423 (M - H)+; Purity (HPLC) 90%, Table 5 Legend to Scheme 6: f) BOC protected anm»» (R4), KjCQa, DMSO; ii) thkphenob (R^-SH), Cu^fOO, DMF; m) NaOAc, oxorte, water; iv) JLTFA, b-HO, rrefcanol INTERMEDIATE 60 fe^-Bntyl4-(2-bromothieno[3^^pyridiii-4-yl)piperazijie-l-carboxyIate 2-Bromo-4-cMorothiKio[3^-c]pyridiiie (5.0 g, 20.24 mmol) and K2CO3 (13.97 g, 101.2 mmol) was sfitred in DMSO (20 mL) followed by addintion of iert-butyl prperazine-1-carboxylate (4.14 g, 22.26 mmol). The reaction mixture was stirred at 100 °C for 6 days. The reaction mixture was filtered to einnmate the carbonate and addition of water (50 mL) and ethyl was followed. The phases were separated and the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried (MgSO,*) and the solvent was evaporated. The crude product was purified by flash chromatography using ethyl acetate/hexanes (2/8) as eluent to give 2 g of the desired product, yield 25%, 99% pure. !H NMR(270 MHz, CDC13) 8 1.48 (s, 9H), 1.52-1.63 (m, 1H), 3.42-3.47 (m, 4H), 3.61-3.64 (m, 4H), 7.22 (dd, J= 5.4,1 Hz, 1H), 7.35 (d, J= I Ez, 1H), 8.04 (d, J= 5.4 Hz, 1H). m/z = 398.91 (M+H), bromide patten. INTERMEDIATE 61 tert-butyI4^2-bromofMeno[3^]pyridin-4-y5-l,4-diazepane-l-carboxj^ate The same procedure above intermediate was used starting from 2-bromo-4- chIoroaieno[3^-c]pyridine (7.5 g, 30.45 mmol), K2C03(6.7 g, 33.5 mmol) and fcrt-butyl 1,4-diazepane-l-carboxyiate (21.0 g, 152.2 mmol) in DMSO (30 mL). Purification by flash chromatography 3.04 g of me title compound (Yield 25%) JJPLC purity 92%; *H NMR (270 MHz, CDC13) 5 1.3S (s, 4.5 H), 1.43 (s, 4.5 H), 1.96-2.11 (m, 2H), 3.36-3.41 (m, 1H), 3.46-3.51 (m, 1H), 3.65-3.S7 (m, 6H), 7.02-7.04 (m, 1H), 7.40-7.42 (m, 1H), 7.94 (d, J= SA Hz, IB). m/zMU.97 (M+H). Coupling with thiopbenols (Method M) INTERMEDIATE 62 tert-batyl4-(2-phenyltbio)tbieno[3^^]pyTidin^yI)-l^iiazepane-l-carbox),late f^-Butyl4-(2-bromotmeno[3^-c]pyridm-4-yl>l,4^azepane-l-carboxylate .(0.31 g, 0.752 mmol), pulverized KOH (0.084 g, 1.5 mmol) and Cu2(I)0 (0.1 g, 0.75 mmol) was mixed with DMF(1 mL) before the addition of asolutionofbenzenetniol(.016g, 1.5 mmoI)inDMF(lmL). The reaction mrxtnre was heated to 120 °C for 15 h. The reaction mixture was poured in a silica plug and elated with chloroform, to give the crude product. The crude product was purified by flash chromatography using ethyl acetate/hexanes (2/8) as eluent to give 0.21 g of the desired product, yield 64%, 90% pure. *H NMR (270 MHz, CDC13) 5 1.37 (s, 4.5H), 1.43 (s, 4J H% 1.97-2.10 (m, 2H), 3.36-3.43 (m, 1H), 3.46-3.53 (m, 1H), 3.64-3.73 (m, 2H), 3.78-3.96 (m, 4H), 7.05 (d, J= 5.4Hz, 1H), 7.22-732 (m, 5H), 7.59-7.63 (m, IH), 7.97 (d, J= 5.4 Hz, IE), m/z = 442.15 (M+H). Oxidation of thio-derivatrres (Method N) INTERMEDIATE 63 f^-Bntyl4K^phenylsidfoByl)tfaiaio[3^]pyridJn-4-y^l]4-diazepane-l-carboxylate A solution of tert-Butyl 4-(2-j3feerQloM)nneno[3^-c]pyridin-4-yI)-l,4H3iazepane-l-carboxylate (0.21 g, 0.48 mmol) and NaOAc (0.5 g) in etbanol (10 mL), (pH ~5) followed by the addition of Oxone (0.64 g, 1.04 mmol) dissolved in water (1 mL). The reaction mixture was stirred atRT for 16 h. Additional Oxone (0.32 g) in water (ImL) was added. Full conversion of the SM was obtained after 8 h. Water (50 mL) and chloroform (30 mL) were added. The phases were separated and the aqueous phase was extracted with chloroform. The combined organic phases were dried over (MgSOit), the solvent was evaporated to give the crude product which was purified by reverse-phase chromatography (10-+90), to give 0.191 g of the desired product as yellow oil (Yield 86%) 98% pure. lH NMR (270 MHz, CDC13) 5 1.28 (s, 4.5 H), 1.38 (s, 4.5 H), 1.99-2.03 (m, 2H). 3.31-3.40 (m, 1H), 3.42-3.47 (m, 1H), 3.63-3.69 (m, 2H), 3.S5-3.98 (m, 4H), 7.02 (d, J= 5.4Hz, 1H), 7.48-7.61 (m, 3H), 7.76-8.01 (m, 3H), 8.06-8.08 (m, 1H). m/z = 474.01 (M-fH). Removal of tie f-batyl-carboxylate protecting group (Method O) EXAMPLE 83 4-(l,4-Diazerffln-l-yI)-2-(pheiiyIsiilfonyO^™op^c]pyri6^ehydnM^oride taf-Butyl4^2-phenylsalfonyl)&ieno[3^ (0.165 g, 0.348 mmol) was dissolved in DCM (2 mL) and TFA (1 mL) was added. The reaction mixture was stirred for 2 h. The solvent was evaporated. Methanol and HCI in ether was added (x 3) to give 0.118 g of the desired HCI salVyield 85%, 98% pure. 'H NMR (270 MHz, CHOH-d*) 8 2.45-2.52 (m, 2H), 3.45-3.52 (m, 2H), 3.70-3.79 (m, 2H), 4.18-4.22 (m, 2H), 4.30-4.40 (m, 2H), 7.62-7.76 (m, 5H), 7.91 (d, J = 5.4 Hz, 1H), 8.11 (dd, J= 5.4,1 Hz, 1H), 8.41 (d, J= 1 Hz, 1H). m/z = 374.09 (M+H-HC1). INTERMEDIATE 64 i!OT,-BntyI4-[2-(4-fert-bnty^heny0fluo]tMeno[3^Ipyridffl-4-yI)-l,4-diazepane-l- carboxylate The product was prepared according to Method M. Purification by flash chromatography using ethyl acetate/hexanes (2/8) as eluent gave 0.035 g, 99% pure. LH NMR (270 MHz, CDCI3) 6 1.28 (s, 9H), 1.38 (s, 4.5 H), 1.43 (ss 4.5 H), 1.98-2.03 (m, 2H)S 3.35-3.41 (m, IB), 3.46-3.52 (m, 1H), 3.62-3.72 (m, 2H), 3.77-3.93 (4H), 7.04 (d, J= 5.4 Hz, 1H), 7.27-734 (m, 4H), 7.54-7.56 (m, 1H), 7.95 (d, J= 5.4 Hz, 1H). m/z = 498.0 (M+H). INTERMEDIATE 65 fert-Bnf^4-[2-(4-tei^ntyIphenyI)siiUonyl]Meno[3^c]pyridin-4-yI)-l,4-diazepaiie-l- carboxylate Procedure B from tert-butyl 4-[2^4-tert-butylplieQyl)thio]aueiK>[3^<: g mmol oxone naoac in etoh mlibllowed by reversed phase chromatography gave mg of the prodncl yield pure. nmr mhz cdc13 j="10.8" hz m> INTERMEDIATE 66 ^-Bnlyi4-[2-(3.4HlimefiiylphenyI)tMo]t]ueno[3 carboxylste The title compound was obtained according to Method M. Purification by flash chromatography using ethyl acetate/hexanes (2/8) as eluent gave 0.022 g, 95% pure. *H NMR (270MHz, CDCI3) 5 1.38 (a, 4.5 H), 1.43 (s, 4.5 H), 1.96-2.04 (m, 2H), 2.21 (s, 3H), 2.22 (s, 3H), 3.37-3.45 (m, 2H), 3.47-3.50 (m, 2H)5 3.77-3.95 (m, 4H), 7.01-7.12 (m, 3H), 7.16 (s, 1H), 7.53 (dd, J= 5.4,1 Hz, 1H), 7.94 (d, J= 5.4 Hz, 1H). m/z = 470.3 (M+H). INTERMEDIATE 67 terf-Bntyl4-[2-(3,4HiimethyIphenyI)siitfonyI]tM^ \-carboxylate "rocedureB from ferf-Butyl 4-[2-(3,4-dimemylphenyl)tHo]tbieno[3^-c]pyridin-4-yl)-l,4-liazepane-1-carboxyiale (0.022 g, 0.047 mmol); OXONE (0.11 g, 0.19 mmol); NaOAc (0.5 g) inEtOH (2 mL) followed by reversed phase chromatography (40-*70), 9 mg of the product Yield 38%, 92% pure-'H NMR (270 MHz, CDC13) 8 1.35 (s, 9H), 2.08-2.20 (m, 2H), 2.33 (s, 6H), 3.52-3.59 (m, 2H), 3.83-3.88 (m, 2H), 4.08-4.18 (m, 4H), 7.21-7.28 (m, 2H), 7.31-735 (m, IE), 7.73-7.75 (m, 2H), 8.02 (d, J= 5.4Hz, 1H). m/z = 502.21 (M+H). INTERMEDIATE 68 (ert-BalyI4-[2^1-naphthyI)tiiio]thieii(>E3^-c]pyridiii-4-yr)-l'4-t'iazePaiie_i-carboxylate The title compound was obtained according to Method M. Purification by flash chromatography using ethyl acetate/hexanes (2/8) as eluent gave 0.055 g. HPLC purity 99 %; 'HNMR(270 MHz, CDC13) 5 1.37 (a, 4.5 H), 1.43 (s,4.5 H), 1.89-2.20 (m, 2H), 3.30-3.40 (m, 1H), 3.43-3.50 (m, IB), 3.60.3.90 (m, 6H), 6.99 (d, J= 5.4 Hz, 1H), 7.39 (dd, J= 8.1,1 Hz, 1H), 7.50-7.61 (m, 5H), 7.79-7.88 (m, 2H), 7.92 (d, J= 5.4 Hz, 1H), 8.40-8.44 (m, 1H). rh/z = 498.26 (M+H). INTERMEDIATE 69 tert-Bntyl4-[2^1-naphthyl)siilfonyl]thieno[3^-c]pyridiii-4-yl)-l,4-diazepane-l- carboxylate Procedure B from terf-Butyl 4-[2-(l-naphmyl)Qno]thieno[3,2-c]pyridin-4-yl>lJ4-diazepane-1-caiboxylaie (0.055 g, 0.112 romol); Oxone (0.27 g, 0.448 mmol); NaOAc (0.5 g) in EtOH (2 roL) followed reversed phase chromatography (40-»70) gave 15 mg of the product Yield 26%, 93% pure. !H NMR (270 MHz, CDCI3) 8 1.34 (s, 9H), 2.06-2.10 (m, 2H), 3.48-3.62 (m, 2H), 3.78-3.86 (m, 2H), 3.95-4.16 (m, 4H), 7.19-7.31 (m, 2H), 7.60-7.75 (m, 3H), 7.92-7.99 (m, 2H), 8.18 (m, J= 8.1 Hz, 1H), 8.50-8.53 (m, 1H), 8.77-8.80 (m, 1H). m/z = 524.22 (M+H); EXAMPLE 84 4-(l,4-Dia2epan-l-y^2-[(3,4-di(*lorophenyI)siilfoiiyI]flUeno[3^-c]pyridine hydrochloride tert-Bm^ 4-{2-[{3J4-dichlorophenyl)sulfo^ carboxylate was prepared from 3,4-dichloromiophenol (60 mg, 15%), as a beige solid, by the application of the general procedures A and B described above. !H NMR (CDCI3) 5 8.27-8.14 (m, IH), 8.11-8.04 (m, 2H), 7.87-7.80 (m, 1H), 7.67-7.62 (m, 1H), 7.26-7.20 (m, 1H), 4.18-3.98 (m, 4H), 3.87-3.74 (m, 2H), 3.61-3.44 (m, 2H), 2.20-2.00 (m, 2H), 1.33 (s, 9H); MS m/z 542 (M+l).The title compound (50 mg, 95%) was obtained as abeige solid, by the application of the general procedure C described above. !H NMR (270 MHz, CH3OH-d4) 5 8.48 (s, 1H), 8.30 (d, J» 1.85 Hz, 1H), 8.05 (dd, J= 8.58,1.98 Hz, 1H), 7.92 (d, /= 6.86 Hz, 1H), 7.83 (d, /= 8.44 Hz, 1H), 7.69 (d, J= 6.86 Hz, 1H), 4.4.41-4.34 (m, 2H), 4.2+4.16 (m, 2H), 3.76-3.69 (m, 2H), 3.51-3.43 (m, 2H), 2.52-2.42 (m, 2H); MS m/z442(M+l). EXAMPLE S5 4^1,4-Diazepan-l-yI)-2-[l-QaphthylsiiIfoiiyI)diieno[3^c]pyridmehydrocUori(le The title compound was obtained from tert-butyl 4-[2-(l-iiaphtiiyI)sulfoayl]thieno-[3,2-c]pyridin-4-yl)-l,4-dia2epane-l-caiboxylate (15 mg, 0.029 mmol) following Method O to give 12 mg of die desired product yield 90 %, 95 % pure. *H NMR (270 MHz, O^CH-d,) 8 2.40-2.50 (m, 2H), 3.45-3.55 (ro, 2H), 3.65-3.75 (m, 2H), 4.06-4.26 (m, 2H), 4.27-4.46 (m, 2H), 7.58-7.80 (m, 4H), 7.83-7.86 (m, 1H), 8.06 (d, J= 8.1 Hz, 1H), 8.20 (d, J= 8.1 Hz, 1H), 8.48 (s, 1H), 8.53-8.56 (m, 1H),'8.83-8.86 (m, 1). m/z = 424.06 (M+H-HC1). EXAMPLE 86 4-(l,4-Diazepan-l-yl)-2-[4-te«-bHtyIphenylsnlfonyI)fliieao[3^-c]pvridine hydrochloride The title compound was obtained from tert-butyl 4-[2-{4-tert-butylphenyI)-sulfonyljtliietiop^-cjpyridm-^ylj-l^diazepane-l-carboxylate (6 mg, 11.3 mmol) following Method O to give 4 mg of the desired product, yield 76 %, 88 % pure. !H NMR (270 MHz, CH3OH-d4) 6 1.33 (s, 9H), 2.41-2.47 (m, 2H), 3.41-3.49 (m, 2H), 3.65-3.78 (m, 2H), 4.15^25 (m, 2H), 4.29-4.40 (m, 2H), 7.65-7.70 (m, 3H), 7.90 (d, J= 5.4 Hz, 1H), 8.00-8.04 (m, IS), 8.37 (s, 1H). m/z = 430.06 (M+H- EXAMPLE87 4-2-[3,4- hydrochloride The title componnd was obtained from terf-butyl 4-[2-(3,4 drmethylphenyl)- snIfonyI]tMeno[3,2-c]pyridm4-yl)-l,4-d^ following Method O to give 6 mg of the desired product, yield 88 %, 89 % pure. !H NMR (270 MHz, CHjOH-d*) 5 2.34 (s, 6H), 2.45-2.55 (m, 2H), 3.42-3.51 (m, IB), 3.67-3.76 (m, 2H), 4.1Q-42D (m, 2H), 3.58-3.70 (m, 2H), 7.39-7.41 (m, 1H), 7.64-7.67 (m, IK), 1.19-7.84 (m, 2B% 7.89-7.91 (m, IE), 8.36 (s, 1H). m/z - 402.07 (M+H-HCI). EXAMPLE 88 2-[(4-Bromophenyl)siilfonyI]-*-(l,4-diazepan-l-yl)tfaieno[3^-cIpyridine hydrochloride Trifluoroacetic acid (1 mL) was added slowly to a solution of tert-butyi 4-{2-[(4- bromo^henyI)to]tmeno[3,2-c]pyridm^yl}-l^ (26 mg, 0.047 mmol) in CH2CI2 at 0 °C. The reaction mixture was allowed to reach room temperature, stirred &r 40 min and then concentrated in vacuo. The residue was twice re-dissolved in MeOH and concentrated in vacuo. The residue was again dissolved in MeOH and an excess of 1M HC1 in diethyl ether (4 mL) was slowly added to lie solution. Removal of the solvents in vacuo afforded the title compound (21 mg, 91 %) as a yellowish solid. !H NMJR. (270 MHz, CH3OH-64) S 8.41 (s, 1H), 8.06-7.99 (m, 2H), 7.92 (d, J= 6.86 Hz, 1H), 7.87-7.80 (m, 2H), 7.66 (d, J= 6.86 Hz, 1H), 4.38^.31 (m, 2H), 4.22-4.14 (m, 2H), 3.74-3.67 (m, 2H), 3.50-3.42 (m, 2H), 2.51-2.39 (m, 2H); MS m/z 452 (M+l). EXAMPLE 89 2-(PheBybulfonyI)^piperazin-l-yItMeno[3^-c]pyridLaehyoj-ochloride To a stirred solution of terf-butyl 4-[2-^henyithio)thieno[3^H:]pvridm-4-y!]prperazine-l-carboxylate (350 mg, 0.819 mmol) in ethanol was added oxone in water solution. The reaction was monitored by LCMS. When all starting material was consumed, the chromsfogram showed two major peaks, the product and the N-oxide. After purification by preparative HPLC, the resulting Boc-materiai was treated with HC1 in ether. The solution was csanifugated and the supernatant was removed. Ether was added, then centrifagated and decanted (repeated three times) to remove the excess HCL The remaining ether was finally evaporated in a SpeedVac concentrator. Yield 18 %, HPLC purity = 98%, m/z = 360.0 (M+H). 'H NMR (270 MHz, CHjOH-d^ 8 ppm 3.56 (m, 4 H) 4.08 (m, 4 H) 7.68 (m, AH) 7.77 (dd,>&60,0.79Hz, 1H) 8.04 (d,>6.33 Hz, 1H) 8.12 (m, 2H) 8.39 (d, JKJ.79 Hz, 1 H). EXAMPLE 90 2-(3-Meflioiy-beiizenesnIfoDj'I)-4-pq>era2in-l-yi-lMeDo[3^-c]pyridiDe hydrochloride 4-[2^3-Me&o^-phenylsuliaii)^Hln I-carboxylic acid terf-butyi ester was obtained from 3-methoxythiophenol (130 ul, 1 mmol) and tert-Butyl 4-(2-bromo1biOTo[3!2^]pyridin4-yl)p^eraziiie-l-carboxylate (215 mg, 0.52 mmol). 120 mg, 50%) were obtained by the application of the general Method M described above. ]HNMR(270 MHz, CDC13) 6 1.48 (s, 9 H), 3.42-3.51 (m, 4 H), 3.58-3.67 (m, 4 H), 3.74 (s, 3 H), 6.76 (dd, ^=8.18,238 Hz, 1 H), 6.84-6.92 (m, 2 H), 7.16-7.23 (m, 2 H), 7.51 (s, 1 H), 8.04 (d, ^=5.81 Hz, 1H); MS m/z 458 (M+l). The titte compound was therefore obtained from 4-[2-(3-memoxy-pbenylsulfmyl)-lMerK)[3^^]pyridin--4-yl]-piperazine-l-carboxylic acid tert-butyl (7 mg, 7%), after triturating with diethyl ether, as a beige solid, by the application of the general procedures B and C described above. *H NMR (270 MHz, CD3OD) 8 8.31 (s, 1H), 8.09 (d, J = 6.33 Hz, 1H), 7.71-7.62 (m, 2H), 7.59-7.50 (m, 2H), 7.30-7.23 (ra, 1H), 3.98-3.92 (m, 4H), 3.87 (s, 3H), 3.54-3.48 (m, 4H); MS m/z 390 (M+l). EXAMPLE 9] 2-(4-Metbosy-ben2snesnlfony0^P^erazin-l-yI-1iueno[3^]pjTadiiie hydrochloride 4-[2-(4-Me^xy-phenylsulfaByl)-thieQo[3,2-c]pyri 1-carboxylic acid tert-butyl ester was obtained from 4-methoxytbiophenoI (130 uL 1 mmol) and ferf-butyl 4-(2-bromothierK>[3^-c]pvridm-4-yl^^erazine-l-carboxylate (215 mg, 0.52 mmol). 100 mg, 42% were isolated by the application of the general Method M described above. !HNMR(270MHz,CDCh)S 1.48 (s,9H), 3.40-3-47 (m,4H),3.58-3.65 (m, 4 H), 3.79 (s, 3 H)s 6.83-6.89 (m, 2 H), 7.15 (d, J=5.54Hz, 1 H), 7.35 (s, 1H), 7.38-7.43 (m, 2 H), 7.99 (d, >5.81 Hz, 1 H); MS mJz458 (M+l). 4-[2-(4-mefooxy-pheEylsulfmyl)-miOT^ terf-butyi ester was obtained (25 mg, 23%) as a clear liquid by the application of the general procedure B described above. !HNMR (270 MHz, CDCI3) 5 1.48 (s, 9 H), 3.67-3.91 (m, 11 H), 7.01 (d, J = 8.97 Hz, 2H), 7.27-7.37 (m, 1H), 7.93 (d, J = 8.97 Hz, 2H), 8.01-8.19 (m, 2H); MS m/z 490 (M+I). The title compound was thereby obtained following Procedure Q: 'H NMR (CD3OD) 5 8.25 (s, 1H), 8.09-7.89 (m, 3H), 7.69 (d, J = 6.33 Hz, IB), 7.17-7.10 (m, 2H), 4.00-3.93 (m, 4H), 3.87 (s, 3H), 3.55-3.48 (m, 4H); MS m/z390(M+l). EXAMPLE 92 4-Rperazm-1^2-{[4-trinaorometbyI)phenyI]snlfonyl}thieiio[3^-cIpyri(U»ie hydrochloride 2-{[4-{TrifliioTomemyl)phenyI]tmo}-4-^^^ was dissolved in IFA (1.5 mL) at 0°C, stiiredfbr 15 min andH2Oz (100 ^L) was added. The mixture was stirred at room temperature over night NaOH (2 M) was added, extraction with ethyl acetate (3X), washed with brine, dried over NaSC>4, The solvent was removed and the product was purified by preparative HPLC to afford 154.7 mg (86.2 %). ]HNMR(270 MHz, DMSO-dj) 5 ppm 9.79 (s, 1H) 8.56 (s, 1 H) 835 (d, .£=8.44 Hz, 2 H) S.12-8.05 (m, 3H) 7.79 (d, J==6.33 Hz, 1 H) 3.98-3.96 (m, 4H) 3.32-3.31 (m, 4H); LC-MS 428 (M - Hf; Purity (HPLC) 95% EXAMPLE 93 2-[[2^^-B»tylpheny0snlfonyI]^p^erazlB-l-ylthieDO[3^Ipyridmehydnjdiloride The title confound was prepared following Method M-O. Yield: 10.6 mg (6.3 %) of 2-[[2-fert-butv3pbfflyI)sulfonyl]^pipeia2m-l-ylthieno[3^-c]pyridine hydrochloride. H NMR (270 MHz, DMSO-ds) 5 ppm 9.57 (s, 1H) 8.42 (s, 1 H) 8.26-8.22 (m, 1H) 8.06-8.04 (m, 1H)7.68-7.55 (m, 4H) 3.87-3.86 (m, 4H) 3.34-3.33 (m, 4H) 1.51-1.43 (m, 9H); LC-MS 400 (M - Hf; Purity (HPLC) 90%. EXAMPLE 94 2-[(3,4-Dfc&lorophenyI)5nIfQnyI]^pip«razm-l-yltMeno[3^ hydrochloride The title compound was prepared following Method M-O. Yield: 47.9 mg (22.9 %). !H MMR(270MHz,DMSO-ds)Sppm9.36 (s, 1 H) 8.51 (s, 1 H) $M(6,J=2.U Hz, 1 H 8.06-7.94 (m, 3H) 7.70-7.68 (m, 1H) 3.81-3.77 (m, 4H) 3.31-3.29 (m, 4H); LC-MS 427 (M -H)+; Parity (HPLC) 95%. EXAMPLE 95 2-[(4-*^-BniyIpheny0siuTonylJ^pipermin-l-yltMeno[3 Gxone (0.52 g, 0.84 mmol) in water (4 mL), buffered to pH ~ 6 with sodium oxide acetate, was added to 24(4-fert-biitylpbeoyl)aiio]^piperazm4-yl11nem[3^^]pyjidine (0.42 mmol) in etbanol (30 mL). The mixture was stirred in room temperature for 2 h and more oxone (0.52 g, 0.84 mmol) was added. The reaction was stirred over night Water was added to the mixture, extraction with dichloromefhane (2X 20 mL) and the solvent was removed. The products were purified by preparative HPLC. Yield: 41.9 mg (22.0%). 'H NMR(500MHz, CH3OH-d4) 5 ppm 8.38 (s, 1 H) 8.05-8.01 (m, 3H) 7.80 (d,>6.59 Hz, 1 H) 7.71-7.69 (m, 2H) 4.15^1.13 (m, 4H) 3.59-3.57 (4H) 1.37-1.33 (m, 9H); LC-MS 416 (M -H)+; Purity (HPLC) 95%. EXAMPLE 96 2-(l-Naphmykulfonyl)-4-pipera2m-l-ylthieno[3^]pyridinehydrocliloride The title compound was prepared following Method M-O. Yield: 3.4 mg (0.2 %). 'H NMR (270 MHz, DMSO-de) 6 ppm 9.34 (s, 1 H) 8.S2 (s, 1 H) 8.44 (s, 1 H) 8.26-8.06 (m, 5H) 7.79-7.65 (m, 3H) 3.79-3.7S (m, 4H) 332-3.30 (m, 4H); LC-MS 410 (M - H)+; Parity (HPLC) 95%. EXAMPLE 97 2-[(3-FlDoropheoyDsntfonyq-4-pipei-azm-l-ylMeno[3^ hydrochloride 2-Bromo-4-cnlorothieno[3I2-c]pyridme (190 mg, 0.50 mmol) in DMF (1 mL) was added to 3-fluorobenzenetbioI (95.5 mg, 1.0 mmol), KOH (56 mg, 0.2 mmol) and Cu20 (71 mg, 0.5 mmol) in DMF (1 mL). The reaction was heated to 120°C over night. The mixture was filtrated through a silica phig and the solvent was removed. The product was dissolved in TFA (1.5 mL) at 0°C and the solution were stirred for 15 min, IfcOj (100 uL) was added and the mixture was stirred at room temperature over night 2M NaOH was added, extraction with etylacetate, washed with brine and solvent was removed. The product was purified by preparative HPLC. Yield: 30.1 mg (16.1%) !H NMR (270 MHz, DMSO-ds) S ppm 9.34 (s, 1 H) 8.45 (s, 1 H) 8.16 (d, 7=5.69 Hz, 1 H) 7.97-7.93 (m, 2H) 7.76-7.62 (m, EXAMPLE 102 The title compound was prepared following Method M-O. Yield: 16.9 mg (8.8 %). *H NMR(270MHz,DMSO-de) 5ppm9.17 (s, 1 H) 8.29 (s, 1 H) 8.IS-18.15 (m, 1H) 7.94 (s, I H) 7.66 (d, £=5.69 Hz, 1 H) 7.47 (d, ^=7.67 Hz, 1H) 7.32 (d, J==8.16 Hz, 1 H) 3.29 (s, 2 H) 2.42 (s, 3 H) (7H obscured by solvent signal); LC-MS 388 (M - H)*; Purity (HPLC) 99%. EXAMPLE 103 2-l(2-EthylphenyI)salfonyn^-piperazm-l-yltMeno[3^-c]pyridJ!ie hydrochloride The title compound was prepared foUowing Method M-O. Yield:22.6nig(11.2%). 'H NMR (270 MHz, DMSO-de) 5 ppm 9.19 (s, 1H) 8.32 (s, 1H) 8.17 (d, J=5.69 Hz, 1 H) 8.08 (d, >7.92 Hz, 1 H) 7.73-7.66 (m, 2H) 7.52 (t, ^7.67 Hz, 2H) 3.29 (s, 4H) 3.00 (q, >7.34 Hz, 2 H) 1.10 (m, 3 H) (4H obscured by solvent signal); LC-MS 388 (M - H)+; Purity (HPLC) 100%. reaction mixture was stirred fore one more hour at -78 °C and was then allowed to warm to room temperature. The precipitate that had fanned was filtered and washed with ether to give the sulfonate lithium salt (3.59 g, 74 %) that was used in the next step without further purification. 'H NMR (270 MHz, DMSO-ds) 8 ppm 7.26 [s, 1 H) 7.99 (d, >5.54 Hz, 1 H) 8.14 (d, >5.54 Hz, 1H). MS (M-Li+1) 234. Benzylation of sulfmate salts (Method P) To a suspension of lithium 4KMorotineiK)[3,2^]pyridme-2-sulfmate (100 mg, 0.42mrool) in dry DMF (2 mL) was added a benzylbromide (0.83 mmol, 2 equiv.) and me mixture heated wim stirring for 16 h at 110 °C. Analysis fay LCMS showed desired product and no starting material remaining. The mixtore was treated with polystyi^e-thiophenol (200 mg) and was rolled for 16 h. The suspension was filtered washing with further DMF (2mL). This material was reacted further without purification. Nucleophilic substitution of chlorine (Method Q) To a crude solutions of benzylsulfone in DMF (4 mL) are added potassium carbonate (172 mg, 1.25 mmol) and tert-butyl-piperazme-1-carboxylate (155 mg, 0.84 mmol). The resulting mixtures are heated for 16 h at 110 °C. LCMS shows desired compound and no starting material. The reaction mixtures are filtered and then the solvent removed under reduced pressure. The desired compounds are isolated pure following preparative HPLC. BOC-deprotection (Method S) The BOC N-protected piperazine derivatives are dissolved in HC1/ diethyl ether (1 mL, 1.0M) at room temperature and sarred for 16 h. Removal of the solvent under reduced pressure gave the crude hydrochloride salts. Trituration with acetonitrile gives the desired compound as a white solid. INTERMEDIATE 71 Urhjum 4^;UcTOthieno[3^}pyrimTne-2-sulfinate (0.44 mmol) was treated wifti benzylbromide (0.59 mmol) as described in Meinod P above and then reacted fkmer with (fflt-butyl-piperazine-1-carboxylate as described in Method Q, Yield 0.009 g (7 % over two steps). lHNMR(300MHz, CDC13) 5 8.14 (d,>=5.5 Hz 1 H), 7.27-7.40 (m, 5 H), 7.15-7.21 (m, 2 H), 4.45 (s,2 H), 3.50-3.56(m, 4H), 3.40-3.45 (m, 4H), 1.49 (s, 9 H); MS (ESI+) for C23 H27 N3 04 S2 m/z A-1A (M+H)+. EPLC 77%, RT 3.93 min (ACE3 C8 50x4mm, 5-50% acetonitrile in 3 min). reacted further with ferf-butyl-piperaziiie-1 -carboxylate as described in Method Q. Yield 0.023 g (10 % over two steps). Beige solid. lHNMR (300 MHz, CDC13) 5 8.14 (d, /= 6 Hz, 1B), 7.85-7.91 (m, 1 H), 7.61-7.72 (m, 2 H), 7.50-7.60 (m, 1 H), 7.12-7.31 (m, 2 H), 4.74 (s, 2 H), 3.52-3.71 (m, 8 H), 1.50 (s, 9 H); MS (ESI+) for C24 H26 F3 N3 04 S2 m/z 542 (M+H)+. HPLC 85 %, RT2.13min(YMCODS AQ,33x3mm, 10-90% acetonitrile in 3 win). (10 % over two steps). Beige solid. !HNMR (300 MHz, CDC13) 5 8.14-8.18 (m, 1 H), 7.55 (s, 1 H), 6.40-6.45 (m, 1 H), 6.26-6.34 (m, 2 H), 4.39 (s, 2 H), 3.54-3.72 (m, 14 H), 1.50 (s, 9 H); MS (ESI+) for C25 H31 N3 06 S2 m/z 534 (M+H)+. HPLC 69 %, RT 1.99min (YMC ODS AQ, 33x3mm, 10-90 % acetonitrile in 3 min). tort-Butyl 4-[2^enzylsulfonyl)thieno[3,2]pyridiayllpipenzine-l-carboxylate (0.01 g, 0.02 mmol) was treated as described in Method R to give the desired product as a white solid. Yield 0.009 g, (100 %). White solid. !HNMR (300 MHz, DMSO-d6) 5 8.98 (s, 1 H), 8.13-S.20 (d, J=& Hzl H), 8.00 (s, 1 H), 7.64-7.71 (m, 1 H), 7.18-735 (m, 5 H), 4.93 (s, 2 H), 3.60-3.70 (111,411), 3.22.3.34 (m, 4 H); MS (ESI+) for C18 H19 N3 02 S2 . CI H mh 374 (M+H)+. HPLC 90%, RTZ91min (ACE3 C8 50x4.6mm, 5-50% acetonilrile in 3 mm). INTERMEDIATE 81 fert-Bntyl^2-{[4-(triflnoromethy0beiizyIJsiiIfonyl}thieno[3^c]pyTi(ini^4- y])piperaziDe-l-carbojy]ate Lithium 4^UorotMeno[3^-c]pyridme-2-sulfmate (0.44 mmol) was treated with 4-(triflnoixmerayl)berizy]bromide (0.59 mmol) as described in Method P above and then reacted farther with te?t-butyi-piperazdDe-l-carboxylate as described in Method Q. Yield 0.02 g (16 % over two steps). Beige solid. 'H NMR (300 MHz, CDCh) 6 8.16 (d, J=6 Hzl H), 7.53-7.61 (d, J= 9 Hz 2 H), 7.49 (s, 1 H), 7.26-7.36 (m, 4 H), 4.51 (s, 2 H), 3.49-3.60 On, 4 H), 3.36-3.49 (m, 4 H), 1.49 (a, 9 H); MS (ESI-f) for C24 H26 F3 N3 04 S2 mfz 542 (M+H)+. HPLC 71 %, RT 4.07min (ACE3 C8 50x4mm, 5-50 % acetonilrile in 3 min). EXAMPLE 106 4-P^erazin-l-yl-2-{[4^n^aaromeayI)beBzyIlsalfonyI}diieno[3,2-c]pyriifriie hydrochloride (erf-Bnryl4^2-{[4-(trifluoiX)rnethy^ 1-carboxylate (0.02 g, 0.03 mmol) was treated as described in Method R to give the desired product as a white solid. Yield 0.014 g (100 %) White solid. lH NMR (300 MHz, DMSO-d€) S 925 (s, 1 H), 8.12-8.22 (m, 2 H), 7.66-7.77 (m, 4 H), 7.41-7.52 (m, 2 H), 5.12 (s, 2 H), 322-3.35 (m, 4 H); MS (ESI+) for C19 HIS F3 N3 02 S2. C1H m/z 442 (M+H)+. HPLC 90 %, RT 3.53min (ACE3 C8 50x4.6mm, 5-50 % acetonitrile in 3 min). INTERMEDIATE 82 (^-Bu^-4-{2-[(^bromo&enzy0siiIfonyiIttfeno[3^-cIpyridin^yl}pfperazine-l- carboxylate Lithium 4-cUoro1hieno[3^^]pyridme-2-sulfinate (0.44 mmol) was treated with 3-brcanobenzylbromide (0.59 mmol) as described in Method P above and then reacted further with terf-butyl-piperazine-l-carboxylate as described in Method Q. Yield 0.023 g (10% over two steps). Beige solid. 'HNMRpOOMHz, CDCI3) S 8.16 (d, J=6 Hz, 1H), 7.50-7.55 (m, 2 H), 7.32-7.40 (m, 2 H), 7.10-7.24 (m, 3 H), 4.44 (s, 2 H), 3.61-3.73 (m, 8 H),1.50(s,9H); MS(ESI+)forC23H26BrN3 04 S^ 554 (M+H)+. HPLC 77 %, RT 4.07min (ACE3 C8 50x4.6mm, 5-50 % acetonitrile in 3 min). EXAMPLE 107 2-[(3-Bromobeii7yI)siilfonyl]^piperazm-l-yltUeno[3^^]pyridine hydrochloride tert-Bu^4-{2-[(3--bromobenzyl)8ul^^]^eno[3,2-c]pyri6ii-4-54}pipCTazine-l-catboxylate (0.023 g, 0.04 nmaol) was treated as described in Method R to give the desired product as a white solid. Yield O.013 g (67 %) White solid. 'H NMR (300 MHz, DMSO-6.6) 5 9.19 (s, 1 H), 8.18 (d, J= 6Hz, 1 H), 8.05 (s, 1 H), 7.70 (d,^= 6Hz, 1 H), 7.53-7.58 (rB, 1 HX 7.43-7.45 (m, 1 H), 7.19-7.32 (m, 2 H), 4.98 (s, 2 H), 3.24-3.35 (m, 4 H); MS (ESI+) for CIS HIS BrN3 02 S2 . CI H m/z 452 (M+H)+. HPLC 90 %, RT 3.30mm (ACE3 C8 50x4.6mm, 5-50 % acetonitrile in 3 min). INTERMEDIATE 83 tert-Buryl4-{2-[(3,4-diflnorobenzyi)sntfonyI]tlu^ cftrboxylate ythium 4-chloro1hieno[3^-c]pyridine-2-sul6nate (0.44 mnaol) was treated with 3,4-bis(trifluoromemyl)benzylbromide (0.59 mmol) as described in Method P above and then reacted further with (ert-butyl-piperazine-1-carboxylate as described in Method Q. Yield 0.014 g (6 % over two steps). Beige solid. JH NMR (300 MHz, CDC!;) 5 8.17-8.21 (m, 1 H), 7.71 (s, 1 H), 7.07-7.39 (m, 4 H), 4.59 (s, 2 H), 3.55-3.68 (m, 8 HX 1.49 (s, 9 H); MS (BSI+) for C23 H25 F2 N3 04 S: mh 510 (M+H)+. HPLC 64 %, RT 2,02 mm (YMC ODS AQ, 33x3mm, 10-90 % acetonitrile in 3 min). EXAMPLE 108 2-K2^Diflnorob*nzy9snlfonyI]-4-piperazMi-l-yh^ The BOC group was removed from tert-butyl 4- {2-[(3,4- difluorobeiizyI)sulfonyl]thieno[3^-c]pyridm-4-yl}pipeTazine- 1-carboxyiale using Method R, Yield 0.068 g (100 %). White solid. !HNMR (300 MHz, DMSO-ds) 5 934 (s, I H), 8.22 (s, I H), 8.18 (dJ/=5.5Hz, 1 H), 7.70 (d.^5.5 Hz, 1 H), 7.26-735 (m, 1 H), 7.15-7.22 (m, 1 H), 7.05-7.14 (m, 1 H), 5.08 (s, 2 H), 334-3.42 (m, 4 H), 325-3.34 (m, 4 H); MS (ESI+) for CIS H17F2 N3 02 S2 .ClHm/z 410 (M+H)+. HPLC 90 %, RT 1.07mm (YMC ODS AQ, 33x3mm, 20-50 % acetonitrile in 1.5 min). EXAMPLE 109 2-[(4-Bromoben^l)sii]fonyl}^pipera2iB-l-y^^ lithium 4chloroliiiMio[3^-c]pyridine-2-solfinate (0.42 mmol) was treated with 4-bromobemylbromide (0.59 mmol) as described in Method P above and then reacted Anther wiih rert-butyl-piperazine- 1-caiboxylate as described in Method Q. The BOC protecting group was removed using Method R. Yield 0.024 g (12 % over three steps). White solid. !H NMR (300 MHz, DMSO-46) S S.99 (s, 1 H), 8.18 (d, J± 5.5 Hz, 1 H), 8.02 (s, 1 H), 7.69 (d, J= 5.5 Hz, 1 H), 7.53 (d, J= 8.5 Hz, 2 H), 7.17 (d, ^ 8.5 Hz, 2H), 4.95 (s, 2 H), 3.62-3.68 (in, 4 H), 3.27-3.32 (m, 4 H); MS (ESI+) for CI 8 HIS Br N3 02 S2 . CI H ITIA 454 Qvl+H)+. HPLC 90 %, RT 1.24min (YMC ODS AQ, 33x3mm, 20-50 % acetonitrile in 1.5 min). INTERMEDIATE 84 &^-Bntyl^2-{[23^is(tiTfinoromethy0benzyI|saUonyl}tlueno[3^c]pyridui-4-yI)piperazine-J-carboxylate Lithium 4-cMorothieno[3^-c]pyridine-2-sutfinate (0.44 mmol) was treated with 2,5-bis(tiiQuorome4yI)benzyIbroniide (0.59 mmol) as described in Method P above and then reacted further with fert-biiryl-piperazine-l-carboxylate as described in Method Q. Yield 0.01 g (4 % over two steps). Beige solid. !H NMR (300 MHz, CDCI3) 6 8.16 (d, J= 5.8 Hzl H), 8.00 (s, ] H), 7.74-7.85 (m, 3 H), 4.76 (s, 2 H), 3.56-3.64 (m, 4 H), 3.47-3.56 (m, 4 H), 1.49 (s, 9 H); MS (ESI+) for C25 H25 F6 N3 04 S2 m/z 610 (M+H)+. HPLC 73 %, RT 2.36rnin (YMC ODS AQ, 33x3mm, 10-90 % acetonitrile in 3 min). EXAMPLE 110 2-{[2^Bis(triflnoromethy])benzyI]snlfonyl}^piperazin-l-ylMeao[3^-c]pyTidhie hydrochloride The BOC group was removed from tert-butyl 4-(2-{X2,5-(trifluoroniemyl)-benzyl]sulfonyl}mieno[3^-clpyridin-4-yl)piperazme-l-carboxylate using Method R. Yield 0.024 g (100 %). White solid. !H NMR (300 MHz, DMSO-ds) 5 9.30 (s, 1 H), S.25 (s, 1 H), 8.19 (d, ^5.5 Hz, 1 H), 8.00-8.07 (m, 2 H), 7.85 (s, 1 H), 7.69 (d, /=5.5 Hz, 1 H), 5.22 (s, 2 H), 3.24-3.33 (m, 4H);MS (ESI4-) forC20H17F6N3 02 S2 . CIHm/z 510 (M+H)+. HPLC 90 %, RT l.OSmiii (YMC ODS AQ, 33x3mm, 30-60 % acetonitrile in 1.5 min). IKTERMEDIATE 85 tert-Bnt^4-{2-f{4-metiyibenzy^alfonyI]tWeno[3>2-cJpyridJn-^yl}piperazine~l- carboxyiate Lithium 4-chioromieaio[3^-c]pyridine-2-sulfiiiate (0.44 mmol) was treated -with 4-memymenzylbromide (0.59 mmol) as described in Method P above and then reacted farther with fert-butyl-piperazme-1-carboxylate as described in Method Q. Yield 0.005 g (3 % over two steps). Beige solid. *H NMR (300 MHz, CDCh) S 8.15 (d, J= 6 Hz 1 H), 7.40 (s, 1H), 7.00-7.16 (m, 4 H), 4.42 (s, 2 H), 3.46-3.60 (m, 4 H), 3.37-3.46 (m, 4 H), 2.34 (s, 3 H), 1.49 (s, 9 H); MS (ESI+) for C24 H29 N3 04 S2 m/z 488 (M+Hf. HPLC 69 %, RT 2.06min (YMC ODS AQ, 33x3mm, 10-90 % acetonitrile in 3 min). EXAMPLE 111 2-[(4-MethyIbenzyI)sm^0Byl]^piperaziB-l^ The BOX! group was removed from tert-butyl 4-{2-[(4-methyIbenzyI)sulfbnyl]thienQ[3.2-c]pyridni-4-yl}pipera2ine-l-carboxylate using Method R. Yield 0.05 g (75 %). "White solid. 1HNMR(300MHz,DMSO-d6) 8 9.18 (s, 1 H), 8.17 (d,^=5.5 Hz, 1 H), 8.01 (s, 1 H), 7.67(d,J=5.5Hz, 1 H), 7.3S (s, 3 H), 7.19 (s, 2 H), 7.11 (s, 1 H), 7.00(s, 3 H),4.36(s, 2 H); MS (ESI+) for C19 H21N3 02 S2 . CI H m/z 388 (M4-H)+-HPLC 90 %, RT 1.65 min (ACE3 C8 50x3.0mm, 10-97 % acetonitrile in 3 min). INTERMEDIATE 86 ^-BBtyI442-{[5-cbloro-2- yI)piperaane-l-carboxyIate Litfaiom 4-cMorolMerio[3^-c]pyridme-2-sulrmate (0.44 mmol) was treated with 5-chkiro-2-(trifluoromethyl)benzylbromide (0.59 mmol) as described in Method P above and then reacted farther with (ert-butyl-piperazme-1-carboxylate as described in Method Q. Yield 0.019 g (7.5 % over two steps). Beige solid. JH NMR (300 MHz, CDCh) 6 8.12-S. 14 (m, I H), 7.80-7.88 (m, 2 H), 7.47-7.66 (m, 2 H), 4.71 (s, 2 H), 3.74-3.S3 (m, 4 H), 3.63-3.72 (m, 4 H), 1.49 (s, 9 H); MS (ESI+) for C24 H25 CI F3 N3 04 S2 mft 576 (M+H)+. HPLC 74 %, RT 2.30mm (YMC ODS AQ, 33x3mm, 10-90 % acetonitrile in 3 mm). EXAMPLE 112 2-{[5-Oitoro-2^trifluoromethyI)benzyi]ndfonyI}-4-pipei^Hfl-l-yltlueno[3^2-c]pyridine hydrochloride The BOC group was removed fiom terf-butyl 4-(2-{[5-chloro-2- (triflnorome&yl)beiizyl3sulfb^^ Method r. Yield 0.012 g (92 %}. White solid. ]H NMR {300 MHz, DMSO-ds) 8 9.05 (s, 1 H), 8.18-8.23 (m, 2 H), 7.78-7.83 (m, 1 H), 7.72-7.76 (m, 1H), 7.69 (d, J=6.5 Hz, 1H), 7.62-7.65 (m, 1 H), 5.07 (s, 2 H), 3.65-3.72 (m, 4 H), 7.25-7.34 (m, 4H); MS (ESI+)for C19 H17 CI F3 N3 02 S2 . CI H m£ 476 (M+H)+. HPLC 90 % RT1.65 min (ACE3 C8 50x3.0mm, 10-97 % acetonitrile in 3 min). INTERMEDIATE 87 (^-Bntyl4^{2-I(3^-dimethox>1>enzyI)sntfonyI}^eiio[3,2-c]pyridin-^yI}piperazuie-l- carboxylate Lithium 4-cMorotb^o[3^-c]pyridrne-2-siilfinate (0.44 mmol) was treated with 3,5-dmiethoxybenzylbromide (0.59 mmol) as described in Method P above and men reacted further with tert-bufyl-piperazme-l-carboxylate as described in Method Q. YieJd 0.02 g (10 % over two steps). Beige solid. !H NMR (300 MHz3 CDCb) S 8.14-8.18 (m, 1 H), 7.55 (s, 1 H), 6,40-6.45 (m, 1 H), 6,26-6.34 (m, 2 H), 439 [s, 2 H), 3.54-3.72 (m, 14 H), 1-50 (s, 9 H); MS (ESI+) for C25 H31N3 06 S2 m/z 534 (M+H)+. HPLC 69 % RT 1.99min (YMC ODS AQ, 33x3mm, 10-90 % acetonitrile in 3 min). EXAMPLE 113 2-[(3^DmiettoxybeiizyI^iilfonyl]-4-piperazni-l-yltUeno[3^c]pyridine hydrochloride The BOC group was removed from tert-butyl 4-{2-[(3,5- dimethoxybenzyl)sulfonyl]tbieno[3,2-c]pyridm-4-yl}piperazm Melbod R. Yield O.Olg (62%). White solid. 'H NMR (300 MHz, DMSO-d6) S 9.09 (s, 1 H), 8.18 (d,J=6.7Hz, 1 H), 8.02 (s, I H), 7.69 (d,> 6.7Hz, IH), 6.45-6.48 (m, I H), 635-6.38 (m, 2 H), 4.84 (s, 2H), 3.61-3.67 (m, 4H), 3.58 (s, 6H), 3.24-3.33 (m, 4H).MS (ESI+) for C2CH22N3O4S2m/z 434 fM+H)+, HPLC 90 %, RT 3.60 min (ACE3 C8 50x3.0mm, 10-97 % acetonitrile in 3 min). EXAMPLE 114 2-[(2-NapiithylmethyI)siilfoayII^piperazin-l-yltMeno[3^]pyridiDehydrocUoride 2-(Bromomemyl)Daphthalene was used according to Method P-R to give 12.4 mg of me desired prodnct 'H NMR (270 MHz, CH3OH-d4) 8 ppm (obscured by CH3OEL 4H) 3.70-3.79 (m, 4 H) 4.95 (s, 2 H) 7.36-7.58 (m, 3 H) 7.70-7.91 (m, 6 H) 8.02 (d, >6.60 Hz, 1 H). MS (M+l) 424. EXAMPLE 115 4-Piperazin-l-yl-2-{[4^1^^1iiiBdiazoI^yI)beiizyi]salfonyl}^eBoI3^]pyridine hydrochloride 4-[4-(ETOmomethyl)phenyl]-l^,3-thiadiazole was used according to Method P-R to give 4.8 mg of the desired product *H NMR (270 MHz, CHjOH-ii) 8 ppm 3.41-3.50 (m, 4 H) 3.54 (s, 2 H) 3.89-3.98 (m, 4 H) 7.45 (d,>8.44 Hz, 2 H) 7.75 (d, ^6.33 Hz, 1 H) 7.96- 8.13 (m, 4 H) 9.31 (s, 1 H). MS (M+l) 458. EXAMPLE 116 l-(4-Pyrrolidin-l-ylphenyI}-2-t(4-p^eiudne-l-yl^eno[3^^1pyridin-2-yI)siiIfonvI] ethanone hydrochloride 2-Bromo-l-(4-pyrroUdin-l-y^henyf)ethanoriewasusedaccordmgtoMeftod P-R to give 19.6 mg of the desired product *H NMR (270 MHz, CHsOH-d^ 8 ppm 2.02-2.12 (m, 4 H) 2.69 (s, 1H)3.37 (t, J=6.73 Hz, 4H)3.54 (s, 1 H) 3.56.3.64 (m,4H) 4.124.22 (m,4H) 6.55 (d, J=B.97 Hz, 2 H) 7.78-7.90 (m, 3 H) 8.03 (d, .£=6.86 Hz, 1H) 8.41 (s, 1 H). MS (M+l) 471. EXAMPLE 117 l-[4-(DM&yIaniiiiio)pfaeByJ]-2-K4-piperazme-l-y^ ethaaoM hydrochloride 2-BnjEK>-l-[4-(di^iylanjino^ffl]y3]^iaDffl3e ethanone was used according to Method P-R to give 9.0 mg of the desired product lH NMR. (500 MHz, CEbOH-d*) 6 ppm 1.16 (t, ^=7.06Hz, 6 H) 3.49-3.66 (m, 10 H) 4.144.27 (m, 4 H) 7.13 (br.s, 2 H) 7.S5 (d, >6.59 Hz, 1H) 7.98 (d, >8.48 Hz, 2 H) 8.03 (d, ^6.59 Hz, 1 H) 8.47 (s, 1 H). MS (M+l) 473. EXAMPLE 118 1^4-Bnimop&eayI)-2-[(4^iperaziD-l-yftfueDO[3»2^Ipyridln-2-j1) satfonylj etaanone 2-Bromo-l-(4-bromophenyl)ethanone was used according to method A to give 3.4 mg of the desired product 'HNMR (270 MHz, CH3OH-d*) S ppm 3.55 (s, 2 H) 3.56-3.67 (m, 4 H) 4.0S-4.26 (m, 4 H) 7.68 (d, J==8.44 Hz, 2 H) 7.79-7.98 (m, 3 H) 8.06 (d, .£=6.60 Hz, 1 H) 8.45 (s, 1 H). MS (M+l) 4S1. EXAMPLE 119 lKS^eftoxyphenylVT-K^p^erazin-l-yltluenoISj^cIpyrldiii-^-yl) solfonyl) ethanone 2-bnxno-l-(3-methoxypheQyl)emanone was used according to method A to give 1.0 mg of the Asired product JH NMR (270 MHz, CH3OH-d4) 5 ppm 3.54 (s, 2 H) 3.55-6.62 (m, >10.03 Hz, 4H) 3.82 (s, 3 H)4.06-4.18 (m, 4 H) 7.20 (dd,.7=8.05,2.24 Hz, 1H) 7.34-7.49 (m, 2 H) 7.57 (d, J=739 Hz, 1 H) 7.84 (d, ^=6.60 Hz, 1H) 8.06 (d, ^6.60 Hz, 1 H) 8.41 (s, 1H). MS (M+l) 432. EXAMPLE 120 l-P!ieHyi-2-K4^piperazhi-l-yhhienol3^-clpyridin-2-yI)siilfonyI]etliaiione 2-Bromo-l-phenylemanone was used according to method A to give 1.2 mg of the desired product *H NMR (270 MHz, CH3OH-O4) 6 ppm 3.55 (s, 2 H) 3.57-3.66 (m, 4 H) 4.10-4.24 (m, 4 H) 7.46-4.57 (m, 2 H) 7.66 (t ^=7.39 Hz, 1H) 7.86 (d, >6.60 Hz, 1 H) 8.02 (dd, J=U.\2,6.99 Hz, 3 H) 8.46 (s, 1 H). MS (M+l) 402. Legend to Scheme 8: i) Elhylchlorofbnnaie, TEA, acetone, NaN3; if) BujN, DCM and d^hecylefher; m) POCU, NaOH; iv) BOC protected amines (R4), KJCOJ, DMSO; v) NHa gas Na, NH«C1, THF vi) Sulphonyl chlorides (R1), NaH, THF; vii) HCl/diethyl ether, methanol INTERMEDIATE 88 (2E)-3-(l-Ben2yl-lH-pyiT0l-2-yI)aciyloyl azide To a mixture of l-ben2yMH-pyirole-2-carbaldehyde (28.4g, 0.125mol) and TEA (13.5 mL, 0.187 mol) in acetone (300 mL) was added emylchlorofonnate (17.9 mL, 0.S7 mol) dropwise. The reaction was stirred for 1.5 b after which NaN3 (13 g, 0.200 mol) in H2O (100 mL) was added. After 2h, the reaction was diluted with water and left overnight The acetone was removed and the product was filtered off to afford 21.4 g of a light brown solid. This compound was taken to the next step. INTERMEDIATE 89 l-Benzyl-l,5-dihydro-pyrrolo[3^-c]pyridin-4-one was prepared by the literature procedure according to C. Ducrocq; E. Eisangi; J-M, Lnoste; J. Mispelter; Tetrahedron, Vol 32, pp 773-780, (1976). To a stirred solution of n-tributylamine (30 mL) in diphenyl elher (150 mL) heated to 195 °C was slowly added during 30 minutes a solution of the acyl azide dissolved in DCM (ISO mL). The reaction mixture was stirred at 195 °C for 1 hour and men cooled to room temperatare. Pentane (1.0 L) and ether (1.0 L) was added to the reaction mixture and the precipitate was collected by filtration. The crude solid was triturated with ether to give 6.89 g(81%)ofthepureproduct PurityHPLC>95%;MS (ES])m/z225 (m+H); 'HNMR (DMSO-d6,25 °C, 270.16) 8 10.84 (br s, 1 H), 7.43-7.14 (m, 6 H), 7.00 (d, J = 7.12 Hz, 1 H), 6.57-649 (m, 2 H), 5.83 (s, 2 H). INTERMEDIATE 90 l-BenzyW-chloro-lH-fndole POCIj (3.11 mL, 33.4 mmol) was added to i-benzyi-l,S-aftydro-4H-pyrroio[3,2-c]pyridin-4-one (3.75 g, 16.7 mmol) and me reaction was stirred at 120°C for 2L NaOH (1M) was added and the mixture was extracted with DCM three times. The organic layers were dried (MgSO^), filtered and the solvent was removed Flash chromatography (DCM/Heptane/MeOH 4:15:1) gave 1.17 g (29 %) of product. The product was taken to the next step. INTERMEDIATE 91 tert-Batyl 4-(l-benzyI-lH-pyrn)lo[3^c]pyridin-4-y0p^er«2me-l-carborylate A mixture of l-benzyl-4-chloro-lE-inaole (1.17 g, 4.82 mmol), K2CO3 (2.0 g, mmol) and Boc-piperazine (1.79 g, 9.64 mmol) in DMSO (75 mL) was stirred at 120 °C for 48 h. Additional of Boc-piperazine (4 equiv.) was added and the reaction was run for another 48 h. The reaction was diluted with ethyl acetate (200 mL) and the mixture was washed with several portions of water. Flash chromatography {DCM/MeOH/Heptane 4:1:15) gave 0.51 g of starting material and 0.38 g of product 1HNMR (CD3OD) 8 7.87-7.85 (m, 1H), 7.25-7.24 (m, 313), 7.04-6.98 (m, 3H), 6.73-6.71 (m, 1H), 633-6.52 (m, 1H), 5.19 (s, 2H), 3.63-3.59 (m, 8H), 1.47 (s, 9H); MS (ESI) 393 (M + H)+; Purity (HPLC, column ACE) 95% INTERMEDIATE 92 fert-Bntyl 4-( lH-pyrrolo[3^-c]pyridin-4-yI)pipera2ane-l-carboxylate fert-Butyl 4^I^enzyi-IH^yrroIo[3^]pyiidin^yl)piperazine-I^aiboxyl3te (3$3 mg, 0.488 mmol) was dissolved in THF (6 mL) and liquid ammonia (10 mL) in a 30 mL vial. Na (67 mg, 2.93 mmol) was added in portions and me reaction turned violet After 30 min NKjCl (sat) was added and the reaction was let to room temperature The THF was removed and the residue was extracted with DCM. Rjecrystallization (DCM/Heptane) gave 112 mg of a white solid. 1HNMR (CD3OD) 5 8.66 (s, 1H), 7.89 (d, 1H, J = 5.80 Hz), 7.13-7.II (m, 1H), 6.89-6.86 (m, 1H), 6.57-6.56 (m, IH), 3.67-3.60 (m, 8H), 1.48 (s, 9H); MS (EST) 303 (M + H)+; Purity (HPLC, column ACE) 95%. Method S for sulphonylation: ferf-butyl 4H^ff-pyiroIo[3,2-c]pyridm-4-yI)pipera2ine-i-carboxylate (total 1.391 mmol, 1 equiv.) dissolved in THF (14 mL) and dispense to 10 mL vials with screwcap. A suspension of NaH ( 0.1488 mmol, 1.5 equiv.) in THF (15 mL) was dispense evenly to the vials containing the solution of ferf-butyl 4-(Lff-pyiroIo[3,2-cjpyridin-4-yI)prperazine-l-carboxylate and stired for approximately for 15 min. Different sulfonylchlorides were dissolved in THF (2 mL) each and added drop-wise to the reaction mixtures. The reactions were quenched with MeOH (100 fiL) and PS-Trisanrme (3 equiv.) was added to each vial and shake for 2 hours. The mixtures were filtered and the filtrates were concentrate under vacuum. The products that were not pure enough ( Purity 90% pure were collected and concentrated. Method T BOC deprotection; The Boc-protected compound was dissolved in MeOH (2 mL) and HCL/ether (2 mL) was added After 45 min the solvent was removed. INTERMEDIATE 93 i^-BntyM-[l carboxylste Purification fay recrystallization gave 16 mg (56 %) after Boc-deprotection. 1HNMR (CDCb) 5 8.03-8.01 (m, 1H), 7.89-7.86 (m, 2H), 7.57-7.39 (m, 5H), 6.67-6.64 (m, 1H), 3.55-3.52 (m, 8H), 1.47 (s, 9H); MS (ESI) 443 (M + H)+; Purity (HPLC, column ACE) 95%. INTERMEDIATE 94 tert-Botyl^l-[(4-cUorophenyI)salfonyl]-lH^yrrt)lo[3^-c]pyri(Un-4-yl}piperazr[ie- 1-carboxylate Purification by preparative HPLC gave 4 mg (11 %) after Boc-deprotection. 'HNMR (CDC13) 5 8.03-7.51 (m, 7H), 6.89-6.87 (m, 1H), 3.91-3.66 (m, 8H), 1.47 (s, 9H); MS (ESI) 377 CM + H)+; Purity (HPLC, column ACE) 95%. INTERMEDIATE 95 &7t-BntyM-{l-[(4-methoxypheny0suIfottyl}-lH-pyrroIol3,2-clpyridiii-4- yl}piperazme-l-carboxyUte Purification by recrystallization (MeOH/Etoer) gave 21 mg (67 %) after boc-deprotecrioa 'HNMR(CDa3) 8 8.02-8.00 (m, 1H), 7.84-7.80 (m, 2H), 7.48-7.46 (m, 1H), 7.41-7.38 (m, 1H), 6.92-6.86 (m, 2H), 6.64-6.62 (m, 1H), 3.79 (s, 3H), 3.57-3 J2 (m, 8H), 1.48 (s, 9H); MS (ESI) 473 (M + H)+; Purity (HPLC, column ACE) 95% INTERMEDIATE 96 Wr^Bntyl4-(l-{[2-(triflnon)methyI)pheny5siilfonyl}-lH-pyrTolol3^]pyridm-4- yl)piperaziiie-l-carboiylate Purification by preparative HPLC gave 8.6 mg (25 %) after boc-deprotecdon. 1HNMR (CDC13) 6 8.14-8.11 (m, 1H), 8.01-7.94 (m, 2H), 7.89-7.72 (m, 3H), 737-7.34 (m, 1H), 6.89-6.88 (m, 1H), 3.93-3.89 (m, 4H), 3.71-3.67 (m, 4H), 1.47 (s, 9H); MS (ESI) 511 (M + H)+; Purity (HPLC, column ACE) 95%. INTERMEDIATE 97 te?^Entyl4-{l-[(2-methoq'-5-methylphcn5^sidfoD3lJ-lH-pyiTolo[3^-c]pyridiii-4- yl}piperazine-l-carboxylate Purification bypreparative HPLC gave 10.3 mg (32 %) after boc-deprotecuon. !HNMR (CDC13) 6 7.95-7.92 (m, 2H), 7.74-7.72 (m, 1H), 7.44-7.40 (ra, 2H), 6.85-6.77 (m, 2H), 3.92-3.88 (m, 4H), 3.70 (s, 3H), 3.69-3.66 (m, 4H), 2.39 (s, 3H), 1.47 (s, 9H); MS (ESI) 487 (M + H)+; Purity (HPLC, column ACE) 95%. EXAMPLE 121 4-I^razw-l-yI-l-{toluene-4-sQtfonyl)-lH-pyrroIo^ p-Toulenesulfonyl chloride (24.6 mg) was added to tert-bntyl 4^1H-pyn6io[3,2-c]pyriclm-4-yI)prpera2me-l-cart>oxylate the title compound (4.3 mg). LCVMS R?: 1.374 (System 10 ffl 40% MeCN over 1.5 min, ACE CS), Purity. 91%. MS: 357 (M+l) !HNMR (CD3OD) 5 ppm 2.39 (s, 3 H) 3.48 (m, 4 H) 4.06 (m, 4 H) 7.22 (d, J=3J1 Hz, 1 H) 7.43 (d, ^=8.16 Hz, 2H)7.95(m,5H). EXAMPLE 122 1^3-OToro-2-methyi-beiRenesuIfonyI)-4^piperazi]i-l-y^^ hydrochloride 3-Cbloro-2-methylbeiizenesutfonyl chloride (29.0 mg) was added to tert-bvtyl 4-Q.H-pvrrolo[3^-c]pyridin-4-yI)phierazme-l-carDOxylate the title compound (6.3 mg). LCMS RT: 1.563 (System 10 till 40% MeCN over 1.5 min, ACE C8), Purity. 96%. MS: 392 (M+l). EXAMPLE 123 l-(3y4-Diio^o^~beiJzeo«TiKonyl)-4-piperaziB-l-yI-lH-pvrnilo[3^-c]pvridiiie hydrochloride SADimeflioxybenzenulronyl chloride (30.5 mg) was added to /erf-butyl 4-(lff- pyrrolo[3^^]pyridm-4-yI)pq>erazine-l-carboxylate the title compound (8.5 mg). LC/MS Rr: 1-284 (System 10 till 40% MeCN over 1.5 min, ACE CS), Purity. 92%. MS: 404 (M+l) 1HNMR(CD3OD) Sppm3.50(m,>4.21 Hz, 2 H) 3.85 (d, J±322 Hz, 4H) 4.10 (m, >3.96 Hz, 2 H) 7.11 (d, .£=8.66 Hz, 1H) 7.23 (d,^=3.46 Hz, 1 H) 7.48 (d, >1.73 Hz, 1 H) 7.74 (dd, >=8.54,1.86 Hz, 1H) 7.92 (s, 2 H) 8.07 (d, >3.46 Hz, 1 H). EXAMPLE 124 4^4-Piperazin4-yl-pyrn)lo[3^]pyridJne-l-SDlfonyI)-benzoiiitrile hydrochloride 4-Cyanobenzenesul&nyl chloride (26.0mg) was added to tert-butyl 4-(l.H'-pyrrolo[3s2-c]p>ridm-4-yI)piperaziae-l--caiboxylate me title confound (9.1 mg). LC/MS RT: 1.150 (System 10 till 40% MeCN over 1.5 mm, ACE C8), Purity. 93%. MS: 369 (M+l) 1HNMR (CD3OD) 8 ppm3.50(m,4H) 4.08 (m, 4 H)7.29 (d,>3.71 Hz, 2 H) 7.98 (m,4H) 8.29 (d,J=8.66Hz,2H). EXAMPLE 125 1^4^Dichloro-Mophene-2^nlfonyI)^piperaziii-l-yl-lH-pyrrolD[3^-c]pjTidine hydrochloride 4,5-DicMoro-1riiopheiie-2-snlfonyl chloride (32.4 mg) was added to fert-butyl 4-(Lff-pyrrolo[3^-e]pyridm-4-yl)piperazme-l-carboxylate the title compound (0.3 mg). LC/MS RT: 1.119 (System 10 till 40% MeCN over 1.5 rain, ACE C8), Purity. 92%. MS: 418 (M+l). EXAMPLE 126 H2-CMoro^fluoro-benzenesnlfonyl)^pipera hydrochloride 2-Chloro-4-flonrobenzenesulforiyl chloride (29.5 mg) was added to tert-butyi 4-(li?-pyrrolo[3^3pyridiii^yl)pipera2me-l-carboxylate the title compound (2.4 mg). LC/MS RT: 1.361 (System 10 till 40% MeCN over 1.5 min, ACE C8), Purity. 90%. MS: 396 (M+l) 'HNMR (CD3OD) 8 ppm 3.51 (m, 4 H) 4.08 (m, 4 H) 723 (dd, J"=3.96,0.49 Hz, I H) 7.47 (m, 1H) 7.55 (dd, J==8.41,2.47 Hz, 2 H) 7.62 (d, J==6.93 Hz, 1H) 7.91 (d, J=7.1S Hz, 1 H) 8.06 (d, >3.96 Hz, 1 H). EXAMPLE 127 1-PhenylmethaiiesiilfonyM-piperaziii-l-jl-IH-pyiTOIo [3,2-clpyridine hydrochloride I^enyl-memanesulfonyl chloride (24.6 mg) was added to tert-butyl 4-(I_ff-pyrroIo[3J2-c]pyridin-4-yI)piperazirie-l-carbQxylate the title compound (0.2 mg). LC/MS RT: 1.007 (System 10till40% MeCN over 1.5 mm, ACE C8), Purity. 90%. MS: 357 (M+l). EXAMPLE 128 1^5-CMoi^tluophene-2^iilfonyl)^piperazni-l-yl4H-pyrrol()[3^-.c]pyridiBe hydrochloride 5-Chloromiophene-2-salfonyl chloride (28.0 mg) was added to ferf-butyl 4-(lH-pyrrolo[3^^]pyridin-4-yI)piperazine-l-carboxylatethe title compoimd (7.2 mg). LC/MS RT: 1.381 (System 10 till 40% MeCN over 1.5 min, ACE C8), Purity. 97%. MS: 483 (M+l). EXAMPLE 129 1^4-Bntyl-b€iizenesnIfonyI)^piperazin-l-yM 4-N-Bu1yIbeiizenesulfonylcliloride (30.0 mg) was added to tert-butyl 4-(Lff-pyrroIo[3^-c]pyridin-4-yl)prperaziiie-l-carboxykte the title compound (11.9 mg). LC/MS RT: 1.904 (System 10 till 40% MeCN over 1.5 min, ACE C8), Purity. 95%. MS: 400 (M+l) 3HNMR (CD3OD) S ppm 0.90 (t,>7.18 Hz, 3 H) 1.31 (m, 2 H) 1.55 (m, 2 H) 2.67 (m, 2 H) 3.50 (m, 4 H) 4.09 (m, >3.96 Hz, 4 H) 7.25 (d, >3.71 Hz, 2 H) 7.44 (d, ^8.16 Hz, 2 H) 7.91 (m,2H)8.Q2(m,2H). EXAMPLE 130 l hydrochloride (4-Phenoiy)benzene)sulfonyl chloride (34.7 mg) was added to terf-butyl 4-{\H-pynolo[3^1pyridm^yl)piperazuie-l-carboxylate the tide compound (12.8 mg). LC/MS RT: 1.839 (System 10 till 40% MeCN over 1.5 min, ACE C8), Purity. 95%. MS: 436 (M+l) 'HNMR (CD3OD) 8 ppm 3.50 (m, .7=3.96 Hz, 4 H) 4.09 (m, J=4A5 Hz, 4 H) 7.05 (dd, ^8.16, 6.43 Hz, 2 H) 7.26 (m, 2 H) 7.44 (t, >7.79 Hz, 2 H) 7.90 (m, 3 H) 8.01 (d, >3.71 Hz, 2H) 8.07 (d, J=8.91 Hz, 2H). EXAMPLE 131 l^henyIsnMonyI)-4-pipera2iii-l-j'l-lH-pyrroIo[3^-c]pyridine hydrochloride Purification by recrystaHization gave 16 mg (56 %) after Boc-dsprotection. MS (ESI) 343.1 (M + H)+; Purity (HPLC, column ACE) 94%. EXAMPLE 132 l-[(4-Chlorophenyi)siilfonyI]-4^ipei^ziii-l-yl4H-pyrrolo[3^-c]pyridme hydrochloride Purification by preparative HPLC gave 4 mg (11 %) after Boc-deprotectiorL MS (ESI) 377 (M + H)+; Purity (HPLC, colunm ACE) 96%. EXAMPLE 133 H(4-Me&oxyphenyI)snlfoiiyI]^pq>erazm^ hydrochloride Purification by recrystallization (MeOH/Etfaer) gave 21 mg (67 %) after Boc-deprotectkm. MS (ESI) 373 (M + H)+; Purity (HPLC, column ACE) 92% EXAMPLE 134 l-[(2-Metho^-S-methyIpheny0sntfooyl]^piperazin-l-yl-lH-pyrro]o[3,2-cJpyridhie hydrochloride Purification by preparative HPLC gave 10.3 mg (32 %) after Boc-deprotection. MS (ESI) 387 (M + H)*; Purity (HPLC, column ACE) 95%. EXAMPLE 135 4-PhMra^-l-yl-lH[2KtiirhioromeftyOphenyIIsiilfonyl}-lH-pyrrolo[3^Jpyridnie hydrochloride Purification by preparative HPLC gave 8.6 mg (25 %) after Boc-deprotection. MS (ESI) 411 (M + H)+; Purity (HPLC, colunm ACE) 94%. BIOLOGICAL TESTS The abiKty of a compound according to the invention to bind a 5-HTg receptor, and to be pharmaceutically useful, can be determined using in vivo and in vitro assays known in the art. (a) 5-HTe binding Assay Binding affinity experiment for the 5-HTg receptor are performed in HEK293 cells transfected with 5-HTg receptor using (3H)-LSD as labeled ligand according to the general method as described by Boess F.G et aL Neuropharmacology vol 36(4/5) 713-720, 1997. Materials Cell culture The HEK-293 cell line transfected with the 5-HTg receptor was cultured in Dulbeccos Modified Eagles Medium containing 5 % dialyzed foetal bovine serum, (Gibco BRL 10106-169), 0.5 mM sodium pyruvate and 400 ug/ml Geneticin (G-418) (Gibco BRL10131-019). The cells were passaged 1:10, twice a week. Chemkaia The radiofigand \^H\ LSD 60-240 Ci/mmol, obtained from Amersham Pharmacia Biotech, (Buciingfiarnsfcrire, England) was in ethanol and stored at -20°C. The unlabelled ligands, represemng different selectivity profiles, are presented in Table 1. The compounds were dissolved in 100% DMSO and diluted with binding buffo. Disposable Compounds were diluted in Costar 96 well V-bottom polypropylene plates (Coming Inc. Costa, NY, USA). Samples were incubated in Packard Optiplate (Packard Instruments B. V., Gnmingen, The Netherlands). The total amount of added radioligand was measured in Packard 24-well Barex plates (Packard Instruments B.V., Groningen, The Netherlands) in the presence of Microscint™ 20 scintillation fluid (Packard Bioscience, Meridea, CT, USA). Buffer The binding buffer consisted of 20 mMHEPES, 150 mM Nad, lOmMMgCi^and 1 mM, EDTA,pH7.4. Methods Membrane preparation Cells were grown to approximately W)% confluence on 24.5 x 24.5 NUNC culture dishes. The medium was aspirated, and after rinsing with ice-cold PBS, the cells were scraped off using 25 ml Tris buffer (50 mM Tris-HCl, 1 mM EDTA, 1 mM EGTA, pH 7.4) and a window scraper. The cells were then broken with a Polytron homogemser, and remaining particulate matter was removed by low-speed centrifugation, 1 OOOx g for 5 min. Finally, the membranes were collected by high-speed centrifugation (20 OOOx g), suspended in binding buffer, and frozen in aliquots at -70QC. Radioligand binding Frozen cell membranes were thawed, immediately rehomogenized with a Polytron homogenizer, and coupled to SPA wheat germ agglutinin beads (Amersbam Life Sciences, Cardiff, England) for 30 min under continuous shaking of the tubes. After coupling, the beads were centrifuged for 10 minutes at 1000 g, and subsequently suspended in 20 ml of binding buffer per 96-well plate The binding reaction was then initiated by adding radioligand and test compounds to the bead-membrane suspension. Following incubation at room temperature, the assay plates were subjected to scintillation counting. The original SPA method was followed except for that membranes were prepared from HHK293 ceUs expressing (he human 5-HTg receptor instead of from HeLa cells (Dinh DM, Zaworski PG, Gill GS, Schlachter SE, Lawson CF, Smith MW. Validation of human 5-HT6 receptors expressed in HeLa cell membranes: saturation binding studies, pharmacological profiles of standard CNS agents and SPA development The Upjohn Company Technical Report 7295-95-064 1995^7 December). The specific binding of [ n]LSD was saturable, while the noo-specific binding increased linearly with the concentration of added radioligand. CS\ LSD bound with high, affinity to 5-HTg receptors. The K The total binding at 3 nM of [^ LSD, the radioligand concentration used in the competition experiments, was typically 6000 dpm, aed the specific binding more than 70%. 5-HT caused a concentration dependent inhibition of f3!!] LSD binding with an over all average Ki value of 236 nM when tested against two different membrane preparations. The inter assay variability over three e^eriments showed a CV of 10% with an average K, values of 173 nM (SD 30) and a HH1 coefficient of 0.94 (SD 0.09). The intra assay variation was 3% (n=4). Ki values for a limited set of reference compounds wim reported binding affinities at 5-HTg receptor are presented in Table 7. AH unlabelled ligands displaced the specific binding of [^ LSD in a concentration-dependent manner, albeit at different potencies. The rank order of potency for the compounds was methiofhepin (2 nM) >mianserm (190 nM) =5-HT (236 nM) >methysergide (482 nM) >mesulsrgide (1970 nM). Protein determination Protein concentrations were determined with BioRad Protein Assay (Bradford MM. A rapid and sensitive method for me quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248-54). Bovine serum albumin was used as standard. Scintillation counting The radioactivity was determined in a Packard TopCount™ scintillation counter (Packard Instruments, Meriden, CT, USA) at a counting efficiency of ar^xirnately 20 %. The counting efficiency was determined in separate sets of experiments. Saturation experiments At least 6 concentrations in duplicates of radioligand (0.1-20 nM of j^H] LSD) were used in saturation experiments. The specific binding was calculated as the difference between total binding and non-specific binding, which was determined as the binding of radioligand Antagonists to the 5-HTg receptor were characterized by measuring inhibition of 5-HT induced increase in cAMP in HEK 293 cells expressing the human 5-HTg receptor (see Boess et al. (1997) Neuropharmacology 36:713-720). Briefly, HEK293/5-HT6 cells were seeded in polylysine coated 96-well plates at a density of 25,000 / well and grown in DMEM (Dulbecco's Modified Eagle Medium) (without phenol-red) containing 5% dialyzed Foetal Bovine Senrm for 48 h at 37°C in a 5% COj incubator. The medium was then aspirated and replaced by 0.1 ml assay medium (Hanks Balance Salt Solution containing 20 mM HEPES, 1.5 mM isobutyhnemylxanrhine and 1 mg/ml bovine serum albumin). After addition of test substances, 50 ^ dissolved in assay medium, the cells were incubated for 10 min at 37°C in a 5% CO2 incubator. The medium was again aspirated and the cAMP content was determined using a radioactive cAMP tit (Amersham Pharmacia Biotech, BIOTRAK RPA559). The potency of antagonists was quantified by detennining the concentration that caused 50% inhibition of 5-HT (at [5-HTJ= 8 times ECso) evoked increase in cAMP, using the formula ICso>Mn=ICW(l-K5HTyEC5o). The compounds in accordance with the invention have a selective affinity to 5-HTg receptors with Kj and ICso^on values between 0.5 nM and 5 uM or display a % inhibition of fS\ LSD £ 20 % at 50 nM and are antagonists, agonist or partial agonist at 5-HTg. The compounds show good selectivity over 5-HTu, 5-BTa,, 5-HT2E, 5-HTa, 5-HTa;. (c) In vivo assay of reduction of food intake For a review on serotonin and food intake, see Blundell, J.E. and Halford, J.C.G. (1998) Serotonin and Appetite Regulation. Implications for me Pharmacological Treatment of Obesity. CNS Drugs 9:473-495. Obese (ob/obj mouse is selected as the primary animal model for screening as this mutant mouse consumes high amounts of food resulting in a high signal to noise ratio. To further substantiate and compare efficacy data, the effect of the compounds on food consumption is also studied in wild type (C57BL/6J) mice. The amount of food consumed during 15 hours of infusion of compounds is recorded. Male mice (obese CSTBL/oTBom-Lep* *°& lean wild-type C57Bl/6JBom; Bomholtsgaard, Denmark) 8-9 weeks witn an average body weight of 50 g (obese) and 25 g (lean) are used in all the studies. The animals are housed singly in cages at 23±leC, 40-60 % humidity and have free access to water and standard laboratory chow. The 12/12-h light/dark cycle is set to lights off at 5 pjn. The animals are conditioned for at least one week before start of study. The test compounds are dissolved in sotvents suitable for each specific compound such as cyclodextrin, cyclodextrin/methane sulfonic acid, polyemylene glycol/methane sulfonic acid, saline. Fresh solutions are made for each study. Doses of 30, 50 and 100 mg kg^day'1 are used. The purity of the test compounds is of analytical grade. The animals are weighed at the start of the study and randomized based on body weight Alzet osmotic minjpumps (Model 200 ID; infusion rate S ^I/h) are used and loaded essentially as recommended by the Alzet technical information manual (Alza Scientific Products, 1997; Theeuwes, F. and Yam, S.L Ann. Biomed. Eng. 4(4). 343-353,1976). Continuous subcutaneous infusion with 24 hours duration is used. The ininipiimps are either filled with different concentrations of test compounds dissolved in vehicle or with only vehicle solution and maintained in vehicle pre-wanned to 37°C (approx. lb). The rmhipumps are implanted subcutaneously in the neck/back region under short acting anesthesia (metofane/enfmrane). This surgical procedure lasts approximately 5 mm. It takes about 3 hto reach steady state delivery of the compound. The weight of the food pellets are measured at 5 p.m. and at 8 p. m. for two days before (baseline) and one day after the implantation of the osmotic minipunrps. The weigh-in is performed with a computer assisted Mettler Toledo PR 5002 balance. Occasional spillage is corrected for. At the end of the study the animals are killed by neck dislocation and trunk blood sampled for later analysis of plasma drug concentrations. The plasma sample proteins are precipitated with methanol, centrifuged and the supernatant is transferred to HPLC vials and injected into the liquid chromatography /mass spectrometric system. The mass spectrometer is set for electrospray positive ion mode and Multiple Reaction Monitoring. A linear regression analysis of the standards forced flrrough the origin is used to calculate the concentrations of the unknown samples. Food consumption for 15 hours is measured for the three consecutive days and the percentage of basal level values is derived for each animal from the day before and after treatment The values are expressed as mean ± SD and ± SEM from eight anirnalg per dose group. Statistical evaluation is performed by Kruskal-Wallis one-way ANOVA using the percent basal values. If statistical significance is reached at the level of p Whitney U-test for statistical comparison between control and treatment groups is performed substituted in position 3 on the pyrrole ring, for use in the treatment or prophylaxis of type II diabetes. Another object of fee present invention is a compound above, and for the case when ring D is a pyrrole ring, P is, of file formula (c) and R3 is of the formula substituted in position 3 on the pyrrole ring, for use in the treatment or prophylaxis of obesity, to achieve reduction of body weight and of body weight gain. Another object of the present invention is a pharmaceutical formulation comprising a compound above as an active ingredient, in combination with a pharmaceutically acceptable diluent or carrier. Another object of the present invention is a pharmaceutical formulation comprising a compound above, and for the case when, rings A and 3 are both phenyl, P is any one of formula (a) or (c) substituted in position 7 on the naphthalene ring, and R3 is substituted in position 1 on the naphthalene ring, as an active ingredient, for rise in the treatment or prophylaxis of a 5-HTg receptor related disorder, such as obesity, type II diabetes, and/or disorders of the central nervous system, to achieve reduction of body weight and of body weight gain. Another obj ect of the present invention is a compound above as an active ingredient, for use in the treatment or prophylaxis of disorders of the central nervous system. Another object of the present invention is a pharmaceutical formulation comprising a compound above, for the case when rings A and B are both phenyl, P is any one of formula (a) or (c) substituted in position 7 on the naphthalene ring, and R3 is substituted in position 1 on the naphthalene ring, and for the case when ring D is a pyrrole ring, P is of the formula (c) and R3 is of the formula substituted in position 3 on the pyrrole ring, as an active ingredient, for use in the treatment or prophylaxis of type II diabetes. Another object of the present invention is a pharmaceutical formulation comprising a compound above, and for the case when ring D is a pyrrole ring, P is of me formula (c) and R3 is of the formula substituted in position 3 on the pyrrole ring, as an active ingredient, for use in the treatment or prophylaxis of obesity, to achieve reduction of body weight and of body weight gain. Another object of the present invention is a method for the treatment or prophylaxis of a 5-HTg receptor related disorder, such as obesity, type H diabetes, and/or disorders of the central nervous system, to achieve reduction of body weight and of body weight gain, which comprises administering to a subject (e.g., a mammal, a human, a horse, a dog, or a cat) in need of such treatment an effective amount of one or more compounds of any of the formulae described above, their salt forms or compositions that include the compounds or their salt forms, and for the case when rings A and B are both phenyl, P is any one of formula (a) or (c) substituted in position 7 on the naphthalene ring, and R3 is substituted in position 1 on the naphthalene ring. Another object of the present invention is a method for fee treatment or prophylaxis of disorders of the central nervous system, which comprises administering to a subject in need of such treatment an effective amount of one or more compounds of any of the formulae described above, their salt forms or compositions that include the compounds or their salt forms. Another object of the present invention is a method for the treatment or prophylaxis of type n diabetes, which comprises administering to a subject in need of such treatment an effective amount of one or more compounds of any of the formulae described, above, their salt forms or compositions that include the compounds or their salt forms, for the case when rings A and B are both phenyl, P is any one of formula (a) or (c) substituted in position 7 on the naphthalene ring, and Rs is substituted in position 1 on the naphthalene Another object of the present invention is a method for modulating 5-HTg receptor activity, comprising administering to a subject in need thereof an effective amount of one ormore compounds of any of the formulae described above, their salt forms or compositions that include the compounds or their salt forms. Another object of the present invention is (he use of one or more compounds of any of the formulae described above, their salt forms or compositions that include the compounds or their salt forms, and for the case when rings A and B are both phenyl, P is any one of formula (a) or (c) substituted in position 7 on the naphthalene ring, and R3 is substituted in position 1 on the naphthalene ring, for the manufacture of a medicament for use in the treatment or prophylaxis of a 5-HTg receptor related disorder, such as obesity, typ e II diabetes, and/or disorders of the central nervous system, to achieve reduction of body weight and of body weight gain. Another object of the present invention is the use of one or more compounds of any of the formulae described above, their salt forms or compositions that include the compounds or their salt forms for the manufacture of a medicament for use in the treatment or prophylaxis of disorders of the central nervous system. Another object of the present invention is the use of one or more compounds of any of the formulae described above, their salt forms or compositions that include the compounds or their salt forms, for the case when rings A and B are both phenyl, P is any one of formula (a) or (c) substituted in position 7 on the naphthalene ring, and R3 is substituted in position 1 on the naphthalene ring, and for the case when ring D is a pyrrole ring, P is of the formula (c) and R3 is of the formula Another object of the present invention is the use of one or more compounds of any of the formulae described above, their salt forms or compositions that include the compounds or their salt forms, and for the case when ring D is a pyrrole ring, P is of the formula (c) and R3 is of the formula substituted in position 3 on the pyrrole ring, for the manufacture of a medicament for use in the treatment or prophylaxis of obesity, to achieve reduction of body weight and of body weight gain. The methods delineated herein can also include the step of identifying that the subject is m need of treatment of obesity, type II diabetes, or disorders of the central nervous system, or in need of reducing body weight and of body weight gain. The invention further relates to cosmetic use of one or more compounds of any of the formulae described herein, for causing loss of weight, as well as cosmetic compositions containing said compounds. Still further, the invention relates to a non-therapeutic metod for impriving the bodily appearance of a mammal, including a human, in which me method comprises orally administering to said mammal one or more compounds of any of me formulae described herein. "An effective amount" refers to an amount of a compound that confers a therapeutic effect on the treated subject The therapeutic effect may be objective (i.e., measurable by some test or marker) or subjective (i.e., subject gives an indication of or feels an effect). For clinical use, the compounds of the invention are formulated into pharmaceutical formulations for oral, rectal, parenteral or other mode of administration. Usually the amount of active compounds is between 0.1-95% by weight of the preparation, preferably between 0.2-20% by weight in preparations for parenteral use and preferably between 1 and 50% by weight in preparations for oral administration. The typical daily dose of the active substance varies within a wide range and will depend on various factors such as, for example, the individual requirement of each patient and the route of administration. In general, oral and parenteral dosages will be in the range of 5 to 1000 mg per day of active substance, preferably 50 to 150 mgper day. Processes for preparation In a further aspect the invention relates to methods of making compounds of any of the formulae herein comprising reacting any one or more of the compounds of the formulae delineated herein, including any processes delineated herein. The compounds of the formulae above may be prepared by, or in analogy with, conventional methods, and especially according to or in analogy with the following methods. The chemicals used in the above-described synthetic route may include, for example, solvents, reagents, catalysts, protecting group and deprotecting group reagents. The methods described above may also additionally include steps, either before or after the steps described specifically herein, to add or remove suitable protecting groups in order to ultimately allow synthesis of the compounds of any of the formulae described above, their salt forms, or compositions that include the compounds or their salt forms, hi addition, various synthetic steps may be performed in an alternate sequence or order to give the desired compounds. Synthetic chemistry transformations and protecting group methodologies (protection and deprotection) useful in synthesizing applicable compounds are known in the art and include, for example, those described in R. Larock, Comprehensive Organic Transformations, VCH Publishers (1989); T.W. Greene and P.G.M. Wuts, Protective Groups in Organic Synthesis, 2nd Ed., John Wiley and Sons (1991); L. FieserandM. Fieser, Fieser and Fieser's Reagents for Organic Synthesis, John Wiley and Sons (1994); and L. Paquette, ed., Encyclopedia of Reagents for Organic Synthesis, John Wiley and Sons (1995) and subsequent editions thereof. The specific examples below are to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever. Without further elaboration, it is believed that one skilled in the art can, based on Ihe description herein, utilize the present invention to its fullest extent. All publications cited herein are hereby incorporated by reference in their entirety. Methods lH nuclear magnetic resonance (NMR) and 13C NMR were recorded on a Broker Advance DPX 400 spectrometer ait 400.1 and 100.6 MHz, respectively. All spectra were recorded using residual solvent or tetramethylsilane (TMS) as internal standard. IE. spectra were recorded on a Perkin-Elmer Spectrum 1000 FT-IR. spectrophotometer. Ionspray mass spectrometry (MS) spectra were obtained on a Perkm-Elmer API 150EX mass spectrometer. Accurate mass measurements were performed on a Micromass LCT dual probe. Preparative HPLC/MS was performed on a Waters/Micromass Platform ZQ system equipped with System A: ACE 5 C8 column (19x50mm), eluents: MilliQ water, MeCN andMilliQ/MeCN/0.1%TFA and systemB: XterraMS C18, 5umcolumn(19x50mm), eluents; MilliQ water, MeCN and NH4HCO3 (lOOmM). Analytical HPLC were performed on Agilent 1100, column: ACE 3 C8 (system A) or column: YMC-Pack (system B), eluents: MilliQ/0.1%TFA and MeCN. Elemental analyses were performed on a Vario El instrument. Preparative flash chromatography was performed on Merck silica gel 60 (230-400 mesh). Table 1 NMR. spectra were obtained on Bruker 500 MHz or JEOL 270 MHz spectrometers at 25°C, and the chemical shift values are reported as parts per million (S). MS spectra were acquired on a 2690 Separation Module (Waters) with a Platform LCZ (Micramass). Flash chromatography was performed on Silica gel 60 (Merck) or LiChioprep RP-18 (Merck). HPLC analysis were accomplished on a HP SeriesllOO, with a GROM-SIL 100 ODS-0 AE column, 4.6x50mm. The HPLC purifications were performed on preparative HPLC/ Mass system using YMC Combi prep ODS-AQ column, 56x20 aim, Gilson pumps, Dynamax UV-1 detector and Finnigan Mass detector. The used eluents were H2O and CH3CN, both with 0.1% TFA. The purity of me compounds was determined by HPLC. Elemental analysis wzs performed at Structural Chemistry Department, Biovitrum AB, Stockholm. Melting points, when given, were obtained on a Bfichi or a Gallenkamp melting point apparatus and are uncorrected. INTERMEDIATE 1 Synthesis of 6-Amino-quinoIine A suspension of 6-nitro-quinoline (8.7 g, 5 mmol), palladium on charcoal (10 %) (0.1 g) in methanol (0.2 L) was hydrogenated at room temperature for 24 with stirring. The catalyst was filtered and me solvent evaporated to yield a yellow solid. Crystallisation from ethyl acetate yielded me pure title compound as a pale yellow solid (3.3 g, 46%). MSm/z: 145 [M+H+]. ^NMR (270MHz, CHCI3-d) 5ppm 3.89 (s, 2H) 6.87 (d, .7=2.64Hz, 1 H) 7.14 (dd, /=8.97,2.64 Hz, 1 H) 7.25 (dd,/=8.44,4.22 Hz, 1 H) 7.88 (dd, .£=7.92,1.58 Hz, 1 H) 7.90 (d, ^8.97 Hz, 1 H) 8.63 (dd, >4.22,1.58 Hz, 1 H). INTERMEDIATE 2 Synthesis of 6-pheaylsuIfanyI-qninolijie A solution of sodium nitrite (1 g, 14 mniol) in water (6 mL) was slowly added to a stirred solution of 6-aiumo-quinolJne (1.44 g, 10 mmol) in sulfuric acid (50 %) (8 mL). The temperature was kept below 5 °C during the addition. The reaction mixture was poured into a solution of potassium hydroxide (9 g, 16 mmol) and thiophenol (1 mL, 9 mmol) in water (30 mL). The reaction mixture was refluxed for 3 h, cooled and extracted with diethyl ether. The insoluble material was eliminated by filtration. During filtration most of the material was trapped in the solid phase. The filtrate was evaporated and the residue was purified by column chromatography (Si02! ethyl acetate:hexane, 1:2) to yield a colorless oil (100 mg, 4% PS: the low yield is due to the loss of the material during the filtration procedure). MS m/z: 238 [M+H+]. !HNMR(270 MHz, CD3C1) 8 ppm 7.34 (m, 4 H) 7.42 (m, 2 H) 7.57 (dd, 7=8.97,2.11 Hz, 1 H) 7.67 (d, .7=2.11 Hz, 1 H) 7.99 (m, 2 H) 8.84 (dd, >4.22,1.58Hz, 1H). INTERMEDIATE 3 Synthesis of 6-benzenesulfonyI-quinoline 1-oxid A solution of m-chloroperbenzoic acid (1 g, 5.8 mmol) in DCM (10 mL) was added to a stined solution of 6-pheny!sulfanylH5uinoIine (0.25 g, 1 mmol) and NaHC03 (0.5 g)in DCM (10 mL). The reaction was left stirring over night, washed with water, NaHC03 solution and evaporated. Trituration of the residue in diethyl ether gave the pure title product as a slightly yellow solid (0.14 g, 30 %). MS m/z: 287 [M+H+], INTERMEDIATE 4 Synthesis of 6-benzenesnIfonyI-4-chIoro-qainoIine A solution of 6-benzenesulfonyI-quinoline 1-oxid (135 mg, 0.47 mmol) in POCI3 (4mL) was heated at 90 °C for 2 h after which the solution was poured on ice, ammonium hydroxide was added and extraction with DCM. The organic phase was dried (NaS04), the volatiles were evaporated and the residue was purified by column chromatography (Si02, ethyl acetaterpetroleum ether, 1:1) to yield a white solid (39 mg, 27 %). MS m/z: 305 [M+H+]. EXAMPLE 1 Synthesis of 6-benzenesuIfonyl-4-piperazin-l-yl-qnhioliiie hydrochloride A solution of Wjenzenesulfonyl-4-cHoio-quraoline (35 mg, 0.11 mmol) and piperazine (0.5 g, 2.5 mmol) in acetonitrile (2 mL) was heated at 80 "C over night. The mixture was extracted with toluene and water. The organic phase was purified by chromatography on silica gel eluted with CHCI3 saturated with NH3 (gas). The pure product was dissolved in ethyl acetate and HC1 (gas) in diethyl ether was added. The resulting oily residue was dissolved in methanol and ethyl acetate and evaporated to yield a white solid (24 mg, 77%). MS m/z: 354 [M+H+]. ]HNMR (270 MHz, CH3OH-D4) 5 ppm 3.52 (m, 4 H) 4.13 (m, 4 H) 7.36 (d, /=7.18 Hz, 1 H) 7.57 (m, 3 H) 8.01 (m, J=1225, 8.54 Hz, 3 H) 8.28 (d, >8.91 Hz, 1 H) 8.63 (d, >6.68 Hz, 1 H) 8.69 (s, 1 H). Legend for Scheme 2: i) NaffluO, PdtPPii^ n-BuOH, BOC-protected diamines; i£) fe«-butyl piperazine-1-caiboxylate or ierHmtyl 1,4-diazepane-l-carboxylate, triethylanane or KiC03, DMSO, thiols; iv) TFA, H^NaOHji^HCL Method A Preparation of thiol derivatives tert-Butyl 4-(6-bromoquinolin-4-yl)-l,4-diazepane-l-carboxylate (0.5 g, 1.23 mmol) was mixed with the thiol (1 equiv.), NaOtBu (2 equiv.), Pd(PPh3)i (0.05 equiv.) and n-BuOH (5 mL) in a reaction tube. N2 (g) was flushed through the mixture for 30 minutes. The reaction mixture was heated to 120°C overnight. The precipitate was filtrated and the reaction mixture concentrated in vacuo. The residue was dissolved in EtOAc and washed with HiO, dried (MgSC>4) and evaporated. Purification by flash chromatography using DCM: MeOH 98:2 as eluent afforded the title product that was used in the next step without further purification. MethodB Oxidation of thiol derivatives to sulphoBe derivatives The appropriate thiophenols derivatives are dissolved in TFA (5 mL) and stirred for 15 minutes at room temperature. H2O2 (2 mL) was added and the reaction was left stirring overnight. The reaction mixtures are evaporated and the residues are portioned between diethyl ether and water. The layers are separated and the water layer is extracted with diethyl ether and made basic by adding NaOH 1M. Extraction with DCM, drying with MgS04 and evaporation gives the free bases of the products which are dissolved in MeOH, excess of HCI/ether (2M) was added and the solvent evaporated The residues are purified on preparative HPLC/MS (Xterra MS CI 8, 5pm column) using a 10 to 40% MeCN-water gradient (containing 0.1% HOAc) over 10 minutes. The pure fractions are pooled and lyophilised. The residues are dissolved in MeOH and treated with excess of HCI/ether (2M). After evaporation of solvent, a solid is obtained and triturated with diethyl ether giving the desired products as HCl-satts, INTERMEDIATE 5 tert-Butyl 4-(6-bromoqainoIin-4-yl)piperazine-l-carboxylate 6-Bromo-4-chloroquinoline (5.0 g, 20.6 mmol), fert-butyl-1-piperazine (4.1 g, 22 mmol), triethylamine (3 mL, 22 mmol) and DMSO (20 mL) were mixed and heated overnight in anoilbathat 100°C. The reaction was cooled and diluted with diethyl ether and washed with water (5x), dried (MgSO^.) and evaporated. The residue was filtered through a short column of silica (2.5-5 %) MeOH in CH2CI2 and evaporated. Yield 8.02 g. (97 %). Brown liquid. HPLC 98 %, RT=3.01 (System Al, 10-97 % MeCN over 3 min). !HNMR (400 MHz, CDCI3) 5 ppm 1.52 (s, 9 H) 3.12-3.17 (m, 4 H) 3.69-3.75 (m, 4 H) 6.86 (d, ^5.0 Hz, 1 H) 7.72 (dd, 7=9.0, 2.26 Hz, 1 H) 7.92 (d, >8.8 Hz, 1 H) 8.14 (d, J=2.3 Hz, 1 H) 8.73 (d, >5.0 Hz, 1 H). MS (ESI+) for CigHizBrNsOz m/z 392.2 (M+H*) EXAMPLE 2 6-[(2-FIuorophenyl)solfonyl]-4-piperazin-l-yIqohioIifle hydrochloride A total amount of 2.25 mmol, of the appropriate thiophenol was used and the reaction was prolonged with 8 hours. The oxidation step was completed after 24 hours at ambient temperature. Purification by column chromatography on silica gel 10-20 % MeOH in DCM gave the free amine that was additionally purified by preparative HPLC. Yield 15 rug (4 %) Yellow solid. HPLC 95 %, RT=2.33 (System Al, 10-97 % MeCN over 3 min). 'HNMR (400 MHz, DMSO-de) 6 ppm 3.30-3.42 (m, 4 H) 3.51-3.62 (m, 4 H) 7.28 (d, ,7=5.27 Hz, 1 H) 7.42 (dd, >10.29,8.78 Hz, 1 H) 7.52 (t, >7.2S Hz, 1H) 7.77-7.84 (m, 1 H) 8.04-8.21 (m, 3 H) 8.62 (s, 1 H) 8.87 (d, J=5.27 Hz, 1 H) 9.82 (br s, 2 H). MS (ESI+) for Ci9HigFN302S m/z 372.0 (M+H4). HRMS for Ci^isFNsOaS: calcd, 371.1104; found, 371.1102. EXAMPLE 3 6-(l-Naphthyl8iiIfonyI>-4-piperazin-l-yk[niiio!iiie hydrochloride A total amount of 2.25 mmol, of the appropriate thiophenol was used and the reaction was prolonged with 8 hours. The oxidation step was completed after 24 hours at ambient temperature. Purification by column chromatography on silica gel 10-20 % MeOH in DCM gave the free amine that was converted to the HCl-sait. Yield 14 mg (4 %). Grey solid. HPLC 95%, RT=2.S4 (System Al, 10-97% MeCN over 3 min). *HNMR (400 MHz, DMSO-ds) 5 ppm 3.33 (s, 4 H) 4.06 (s, 4 H) 7.38 (d, >6.78 Hz, 1 H) 7.65 (d, J^7.53 Hz, I H) 7.69-7.75 (m, 1 H) 7.82 (t, J=7.78 Hz, 1 H) 8.12 (d, J=8.03 Hz, 1 H) 8.21-8.30 (m, 2 H) 8.38 (d, >8.03 Hz, 1 H) 8.56 (t, >8.53 Hz, 2 H) 8.74-8.79 (m, 2 H) 10.05 (s, 2 H). MS (ESI+) for C23H2,N302S mA 404.4 (M+H*) HRMS for C23H21N3O2S: calcd, 403.1354; found, 403.1365. EXAMPLE 4 6-[(3,4-DichIoropbenyl)siilfonyll-4-piperazin-l-ylqiiiiiolhie hydrochloride A total amount of 2.25 rnrno!, of the appropriate thiophenol was used and the reaction was prolonged with 8 hours. The oxidation step was completed after 24 hours at ambient temperature. Purification by column chromatography on silica gel 10-20 % MeOH in DCM gave the free amine which was converted to the HCl-salt giving yellow solid. Yield 15 mg (3 %). Yellow solid.. *H NMR (400 MHz, DMSO- ds) 5 ppm 3.35-3.41 (m, 4 H) 4.06-4.15 (m, 4 H) 7.40 (d, >6.78 Hz, 1 H) 7.93 (d, >8.53 Hz, 1H) 8.04 (dd, >8.53, 2.01 Hz, 1 H) 8.27 (d,.7=9.03 Hz, 1 H) 8.32 (d, >2.01 Hz, 1 H) 8.36-8.42 (m, 1 H) 8.73 (d, .M.51 Hz, 1 H) 8.82 (d, /=6.53 Hz, 1 H) 9.86 (s, 2 H). MS (ESI+) for C]9 Hn Cl2 N3 O2 S m/z 422.2 (M+H*). HEMS for C19H17CI2N3O2S: calcd, 421.0419; found, 421.0422. HPLC 95%, RT=2.69 (System Al, 10-97 % MeCN over 3 min) EXAMPLE 5 6-[(3,5-DunethylphenyI)sulfonyl]-4-piperazin-l-ylqnino!ine hydrochloride The oxidation step was completed after 2 hours at ambient temperature. Purification, by column chromatography on silica gel 10-20 % MeOH in DCM gave the free amine which was converted to the HCl-salt giving grey solid. Yield 0.007 g (2 %). Yellow solid. HPLC 90 %, Rf=2.57 (System Al, 10-97 % MeCN over 3 mm). MS (BSI+) for C21H33FN3O2S m/z 382.2. HRMS for QiH^FNaOiS: calcd, 381.1511; found, 381.1521. EXAMPLE 6 6-[(2-Chloro-6-methylphenyl)snlfoByI]-4-piperazin-l-ylquinoline hydrochloride A total amount of 2.25 mmol, of the appropriatethiophenol was used and the reaction was prolonged with 8 hours. Additional HzOz (1 mL) was added and the reaction mixture was stirred at 50 DC for another 48 hours. Purification, by column chromatography on silica gel 10-20 % MeOH in DCM gave the free amine that was converted to the HCl-salt Yield 33 mg (7.5 %). WHte solid. !H NMR (400 MHz, DMSO-ds) 5 ppm 2.13 (s, 3 H) 2.98 (s, 4 H) 3.72 (B, 4 H) 7.06 (d, J=6.7% Hz, 1H) 7.14 (dd, ,M1.54, 8.03 Hz, 2 H) 7.23 (t, J=7.7S Hz, 1 H) 7.89 (d, J=8.78 Hz, 1 H) 7.94-8.00 (m, 1 H) 8.24 (s, 1 H) 8.45 (d, J=6.7% Hz, 1 H) 9.68 (s, 2 H). MS (ESI+) for C20H20CIN3O2S m/z 402.2 (M+H4). HRMS for C2oH2oClN302S: calcd, 401.965; found, 401.967. HPLC 95%, Rr=2.55 (System AI, 10-97 % MeCN over 3 min). EXAMPLE 7 6-[(4-ChloropheiiyI)salfonyl]-4-piperajdii-l-ylquinomie hydrochloride A total amount of 2.25 mmol, of the appropriate thiophenol was used and the reaction was prolonged for another 8 hours. The oxidation step was completed after 24 h at ambient temperature. Purification by column chromatography on silica gel 10-20 % MeOH in DCM gave the free amine mat was converted to the HCl-salt Yield 14 mg (3 %). Yellow solid. HPLC 95 %, RT=2.66 (System Al, 10-97 % MeCN over 3 min). MS (ESI+) for C,9HifiClN302S m/z 388.2 (M+lf). HRMS for Ci9H,BClN302S: calcd, 387.0808; found, 387.0821. EXAMPLE 8 6-[(2-MethyI,4-teit-bntyl-phenyI)siilfonyl]^piperazin-l-ylquinoIine hydrochloride The oxidation step was completed after 2 hours at ambient temperature. Purification by column chromatography on silica gel 10-20 % MeOH in DCM gave the fee amine which was converted to the HCl-salt giving gray solid. Yield 17 mg (4 %). HPLC 95 %, RT=2.81 (System Al, 10-97 % MeCN over 3 min). MS (ESI+) for C24H29N3O2S m/z 424.2 (M+H*). HEMS for C24H29N3O2S: calcd, 423.1980; found, 423.1969. EXAMPLE 9 6-[(3,4-Dimetliylphenyl)suIfonyIl-4-piperajaii-l-ylqninoline hydrochloride The oxidation, step was completed after 2 hoars at ambient temperature. Purification by column chromatography on silica gel 10-20 % MeOH in DCM gave the free amine which was converted to the HCl-salt. Yield 33 mg (8 %). Yellow solid. 'H NMR (400 MHz, DMSO-ds) oppm 2.27 (d, >6.27 Hz, 6 H) 334 (s, 4H) 4.12 (s, 4H> 739 (dd, >7.40, 2.13 Hz, 2 H) 7.75 (d, .7=7.78 Hz, 1 H) 7.81 6.78 Hz, 1 H) 10.18 (s, 2 H). MS (ESI+) for C2iH23N302S m/z 382.2 (M+H*). HRMS for C21H23N3O2S: calcd, 381.1511; found, 381.1519. HPLC 95 %, Rr=2.54 (System Al, 10-97 %MeCNover3miri). EXAMPLE 10 6-[(2,3-Dichloropheny^suIfonyl]-4-piperazin-l-yIqHittolme hydrochloride A total amount of 2.25 mmol, of the appropriate thiophenol was used and the reaction was prolonged for another 8 hours. The oxidation step was completed after 24 hours at ambient temperature. Purification by column chromatography on silica gel 10-20% MeOH in DCM gave the free amine which was converted to the HCl-salt. Yield 15 mg (3 %). Yellow solid. 'H NMR (400 MHz, DMSO-de) 5 ppm 3.36 (m, 4 H) 4.10 (m, 4 H) 7.42 (d, .7=6.78 Hz, 1 H) 7.75 (t, ,7=8.03 Hz, 1 H) 8.07 (d, .7=8.03 Hz, 1 H) 8.24 (d, .7=9.04 Hz, 1 H) 8.33 (dd, J=13.93, 8.41 Hz, 2 H) 8.70 (s, 1 H) 8.82 (d, /=6.78 Hz, 1 H) 10.00 (s, 2 H). MS (ESI+) for C,9HnCUNj02S m/z 422.2 (M+H*). HRMS for C19HnCliNiOiS: calcd, 421.0419; found, 421.0408. HPLC 95 %, Rr=2.50 (System Al, 10-97 % MeCN over 3 min). EXAMPLE 11 6^l(4-tert-Botylpheiiyr)siiHo^\]-4-r^ tert-Butyl4-{6-[(4-tert-burylphenyl)lhio]qumolin-4-yl}piperazme-l-carboxylate (0.60 g, 1.3 mmol) was dissolved in TFA (12 mL) and stirred for 30 minutes before H202 (0.65 mL, 6.3 mmol) was added. The mixture was stirred for 2 hours and water (5 mL) was added. The mixture was evaporated and the residue was taken up in water and washed with diethyl ether (2x). The aqueous phase was adjusted to pH 10 with 1N NaOH and the mixture was extracted with CH2CI2 (2x), dried (MgSQj) and evaporated. The residue was diluted with CH2CI2 and 1.3 mL 2N HC1 in diethyl ether was added under vigorous stirring add the mixture was evaporated and washed with diethyl ether (2 x) and dried. Yield: 0.40 g (69 %). Grey solid. HPLC 95 %, RT=2.77 (System Al, 10-97 % MeCN over 3 min). !H NMR (400 MHz, DMSO-ds) S ppm 1.23 (s, 9 H) 3.38 (s, 4 H) 4.08 (s, 4 H) 7.39 (d, >7.03 Hz, 1 H) 7.65 (d, J=8.53 Hz, 2 H) 7.96 (d, .7=8.53 Hz, 2 H) S-25 (d, .7=8.78 Hz, 1 H) 8.30-8.36 (m, 1 H) 8.66 (d, J=\ .76 Hz, 1 H) 8.81 (d, >7.03 Hz, 1 H) 9.85 (br. s, 2 H), MS (BSI+) for C23H27N3O2S m/s 410.4 (M+H4). EXAMPLE 12 H(4-IsopropyVphenyI)saVfony\}-4-pipera2iii-l-ylquinoliiie hydrochloride 4-Isopropylthiophenol (0.152 g, 1.0 mmol) was added dropwise to a suspension of tert-butyl 4^6-bromo-quinolin-4-yl)-piperazine-l-carboxylate (0.2 g, 0.51 mmol), Na-t-butoxide (0.192 g, 2.0 mmol) and Pdp>(Ph)3]4 (0.030 g, 0.025 mmol) in ethanol (3 mL) at 90"C and the mixture was stirred for 18 h. The mixture was diluted with THF and filtered through a plug of silica and evaporated. The crude product was dissolved in TFA (5 mL) and stirred for 15 minutes before 30 % H2O2 (1 mL) was added. The mixture was stirred for 2 hours and evaporated. The residue was dissolved in water and washed with CH2CI2 (2x) and 2 N NaOH was added until pH reached 10 and the mixture was extracted with CH2CI2 (3x), dried (MgSCk) and evaporated. The crude product was purified by preparative HPLC 5-95 water/acetonitrile collecting on m/z 395.2. After evaporation the free amine was dissolved in CH2C12 and and excess of HC1 in diethyl ether was added and fte mixture was evaporated. Yield 0.015 g (7 %). 'HNMR (400 MHz, DMSO-d6) 5 ppm 1.17 (d,>7.03 Hz, 6 H) 2.90-3.02 (m., 1H) 3.34-3.42 (m, 4 H) 4.03-4.12 (m, 4 H) 7.39 (d, ,7=6778 Hz, 1H) 7.51 (d, >8.28 Hz, 2 H) 7.96 (d, >8.53 Hz, 2 H) 8.26 (d, >9.03 Hz, 1 H) 8.29-8.36 (m, 1 H) 8.66 (s, 1 H) 8.80 (d, J=6.78 Hz, 1 H) 9.85-9.97 (m, 2 H). HPLC 95%, RT=2.65 (System Al, 10-97% MeCN over 3 min). EXAMPLE 13 4-PiperaziB-l-yl-6-{[4-(triflnoromethyI)phenyI]snlfonyI}qKiiioline hydrochloride 4-Trifluoromethylthiophenol (0.178 g, l.Oxmiiol) was added dropwise to a suspension of tert-butyl 4^6-bromo-quiiiolin-4-yl)--pipeTazirie-l-carboxylate (0.2 g, 0.51 mmol), Sodium-t-butoxide (0.192 g, 2.0 mmol) andPd[P(Ph)3]4 (0.030 g, 0.025 mmol) in efhanol (3 mL) at 90°C and the mixture was stirred for 18h. The mixture was diluted with THF and filtered ihrough a plug of silica and evaporated. The crude product was dissolved in TFA (5 mL) and stirred for 15 minutes before 30 % H2O2 (1 mL) was added. The mixture was stirred for 2 hours and evaporated. The residue was dissolved in water and washed with CHaCla (2x) and 2 N NaOH was added until pH reached 10 and the mixture was extracted with CH2CI3 (3x) dried (MgS04) and evaporated The crude was purified by preparative HPLC 5-95 wate^acetonitrile collecting onm/z 421.1. After evaporation the free amine was dissolved in CH2CI2 and excess of HC1 in diethyl ether was added and the mixture was evaporated. Yield 0,024 g (10%). *H NMR (400 MHz, DMSO-dg) 5 ppm 3.33-3.40 (m, 4 H) 4.134.21 (m, 4 H) 7.42 (d, /=7.03 Hz, 1H) 8.02 (d, J=8.53 Hz, 2 H) 8.25-8.35 (m, 3 H) 8.37-8.53 (m, 1 H) 8.76 (d,/=L76 Hz, 1 H) 8.80 (d, .7=7.03 Hz, 1 H) 9.95-10.05 (m, 2 H). Yellow oil. HPLC 95 %, RT=2.66 (System Al, 10-97% MeCN over 3 min). INTERMEDIATE 6 tert-Botyl4-(6-bromoqaiiiolin-4-yl)-l,4-diazepane-l-carboxyIate 6-Bromo-4-chloroquinoline (3.5 g, 14.5 mmol) was reacted with/ert-butyl 1,4-diazepane-1-caiboxylate (3.7 g, 18.8 mmol) and KaC03 (4 g, 29 mmol) in DMSO at 100 °C overnight. After cooling the mixture was poured into water and extracted with DCM. The organic layer was washed with water, dried (MgSO,0 and evaporated. The residue was purified by flash chromatography using a gradient of EtOAcrhexane 1:1 to 2:1 giving 2.1 g (36 %) of yellow oil. !H NMR (400 MHz, CDC13) 5 ppm 1.47 (d, .7=5.5 Hz, 9 H) 2.08-2.16 (m, 2 H) 3.35-3.44 (m, 4 H) 3.60-3-73 (m, 4 H) 6.87 (d, .7=5.5 Hz, 1 H) 7.69 (dd,7=9.0, 2.0 Hz, 1 H) 7.88 (6, >8.5 Hz, 1 H) 8.16 (s, 1 H) 8.65 (d,.7=5.0 Hz, 1 H). MS (ESI+) for C,9H24BrN302 m/z 406.4 (M+H)+. HRMS (EI) calcd for CigH^rNs: 405.1052, found 405.1045. INTERMEDIATE 7 tert-Btityl-4{3-[(4-tert-bntyIphenyI)aiio]qHinoIiii-5-ylJ-l,4-diazepaiie-l-earboxylate (General Method A) The compound was prepared &x>m tert-butyl 4-(6-bromoqumolin-4-yi)-lj4-diazepane-l-carboxylate (0.5 g, 1.23 mmol) and p-ferf-butylbenzeneihiol (0.2 g, 1.23 mmol). Yield: 0.27 g (44 %) of the title compound. HPLC 89 %, RT: 3.76 min (5-99 %MeCN containing 0.1 % TFA over 3 min). INTERMEDIATE 8 tert-BDtyI-4{3-[(4-isopropyIpbenyl)mio]qi]inolin-5-yl}-l,4-diazep3tte-l-carboxylate (General Method A) The compound was prepared from tert-butyl 4-(6~bromoquinoIin-4-yl)-l,4-diazepane-l-carboxylate (0.5 g, 1.23 mmol) and 4-isopropylbenzenethiol (0.19 g, 1.23 mmol). Yield: 0.27 g (46 %) of the title compound that was used in the next step without further purification. HPLC 89 %, RT: 3.67 min (5-99 % MeCN containing 0.1 % TFA over 3 min); MS (ESI+) for C^jNsCfeS m/z 478.2 (M+H)+. EXAMPLE 14 6-[(4-(ert-Batylphenyl)sulfonyI]-4-(l,4-diazepan-l-yi)qiiinolDie hydrochloride (General Method B) The compound was synthesized from tert-butyl-4{3-[(4-tert-butylphenyl)tHo]quinolin-5-yl}-l,4-diazepane-l-carboxylate (0.27 g, 0.55 mmol). Yield: 20 mg (8 %) of the title compound.; 'H NMR (270 MHz, DMSOde) 5 ppm 1.25 (s, 9 H) 2.31 (br s, 2 H) 3.25 (br s, 2 H) 3.49 (br s, 2 H) 4.11 br s, 2 H) 4.26 (br s, 2 H) 7.16 (d, >7.1 Hz, 1 H) 7.65 (d, >8.2 Hz, 2 H) 7.94 (d, .7=8,2 Hz, 2 H) 8.19 (d, .7=8.7 Hz, 1 H) 8.26 (d, /=8.7 1 H) 8.62 (d, J=63 Hz, 1 H) 8.75 (s, 1 H) 9.65 (br s, 2 H); MS (ESI+) for C24H29N3O2S m/z mi (M+H)+. HPLC 93%, RT: 2.79 min (5-99 % MeCN over 3 min). EXAMPLE 15 4-(l,4-Diazepan-I-yl)-6-[(4-isopropyIpheny0sulfony]]qaiiioliiie hydrochloride (General Method B) The compound was prepared from tert-Butyi-4{3-[(4-isopropylphenyl)mio]qumolin-5-yl}-1,4-diazepane-l-carboxylate (0.27 g, 0.57mmol). Yield: 15 mg (6 %) of the title compound.; !H NMR (270 MHz, DMSO-de) 5 ppm 1.16 (d, ^6.9 Hz, 6 H) 2.31 (br s, 2 H) 2.96(m,lH)3J5(brs,2H)3^9(brs,2H)4.11(bcs,2H)456(bra,2H)7.l6(d, J=6.9 Hz, 1 H) 7.51 (d, =8.2 Hz, 2 H) 7.94 (d, J=%2 Hz, 2 H) 8.18 (d, J=%.1 Hz, 1 H) 8.30 (d, >8.4 Hz, 1 H) 8.62 (d, ^6.1 Hz, 1 H) 8.75 (s, 1 H) 9.62 (br s, 2 H); MS (ESI+) for CMHHNSQJS m£ 410.4 (M+H)+. HPLC 93 %, R?: 2.70 min (5-99 % MeCN over 3 min). INTERMEDIATE 9 7-Bromo-l-ChIoroisoqninoline To phosphorus oxychlctride (46-6 mL, 0.5 raol) at room temperature was added, portionwise, 7-bromo-l-hydroxyisoquinoline (11.2 g, 0.05 mol). The mixture was heated to 100 °C for 90 mis with rapid stirring. On cooling to room temperature, the mixture was poured, cautiously onto ice/water (200 mL). Dropwise addition of aqueous ammonia raised the pH=8 and the resulting precipitate was collected by filtration, washing with cold water. The solid was dried under reduced vacuum at 45 °C for 12 h. 13.86 g (115 %) Beige solid _ isolated. 'H NMR (DMSO-dg) o 8.4 (s, 1 H), 8.34-8.38 (d, J = 6 Hz, 1 H), 8.03-8.07 (m, 2 H), 7.91-7.96 (d, J - 6 Hz, 1 H); HPLC: 96%; LCMS: 242,244,246. Nucleophttic displacement of Chlorine INTERMEDIATE 10 4-(7-Bromo-isoquinolme-l-yI)-piperaziiie-l-carboxylic acid, tert-butyl ester To a suspension of 7-bromo-l-chloroisoquinoline (3.14 g, 1 3mmol)irtDMSO(20mL) at room temperature was added either carboxylic acid tert-butyl (BOQpiperazine (7.23 g, 38.8 mmol) or BOC-homopiperazine (7.77 g, 38.8 mmol) and then potassium carbonate (5.36 g, 39 mmol). The mixture was heated to 110 °C for 24 h. On cooling, the mixture was poured onto ice/water (50 mL) and extracted with ethyl acetate (3 x 50 mL). The combined organic phases were washed with water 50 mL) and brine (50 mL). Before drying over anhydrous sodium sulfate. Removal of solvent under reduced pressure gave crude product. Purification was performed by applying the crude material to a plug of silica in a filter funnel and eluting with heptane/ethyl acetate (2:1) and gave 2.73 g (54 %) yellow oiL 'HNMR(CDCI3) S 8.20-8.22 (m, 1 H), 8.13-8.18 (d,J= 6Hz, 1 H), 7.65-7-71 (dd, /«= 12,3 Hz, 1 H), 7.59-7.65 (d, /= 12 Hz, 1 H), 7.21-7.25 (m, 1 H), 3.64-3.73 (m, 4 H), 7.27-7.36 (m, 4 H), 1.49 (s, 9 H); LCMS: 392,394,395. INTERMEDIATE 11 4-(7-Bromo-isoquinoline-l-yIMl>4]diazepane-l-carboxylic add, tert-butyl ester 2.75 g (52 %) yellow oil isolated :H NMR (CDCb) 6 8.19-8.24 (m, 1 H), 8.06-8,12 (d, J= 9 Hz, 1 H), 7.54-7.68 (m, 2 H), 7.11 (m, 1 H), 3.47-3.74 (m, 8 H), 1.98-2.16 (m, 2 H), 1.48 (s, 9 H); LCMS: 406,407,408. ) Palladium-catalysed aryi thiol coupling To 7-bromo-l-chloroisoquinoline (1 mmol) inbutan-1-ol (20 mL) at room temperature was added sodium fert-butoxide (481 mg, 5 mmol), thiol (1.5 mmol) and tetrakis triphenylphosphine palladium (60 mg, catalytic). The mixture was heated to 120 °C for 16 b. On cooling to room temperature, the mixture was filtered through silica eluting with THF. Removal of solvent under reduced pressure gave the crude product which was used without further purification in the subsequent step. INTERMEDIATE 12 4-[7-(2-CMoro-6-mefhyl-phenylsDlfanyI)-isoqninoIin-l-yl]-piperaziiie-l-carboxy!ic acid fert-bntyl ester Amixtureof4-(7-bromo-isoqumolme-l-yl)-piperazme-l-carboxyUcaci4(ert-butyl ester (0.5 g, 1.3 mmol), 2-chloro-6-mefhyl-thiophenol (0.206 g, 1.3 mmol), NafBuO (0.44 g, 4.5 mmol), Pd(PPh3)4 (74 mg, 0.065 mmol) in nBuOH (10 mL) was heated at 110 °C, 3h. The reaction mixture was filtered. The filtrate was concentrated and the residue was dissolved in ethyl acetate. The organic phase was washed with water (50 mL x 3), separated and dried (MgSOa), filtered. The volatiles were evaporated and the residue was purified by flash column chromatography (SiOz, n-heptane: ethyl acetate 8:2) to give 530 mg of the title compound as colourless oil (yield 86.4 %). 'HNMR (CDCh) 5 8.05 (d, 1H), 7.65 (d, 1H), 7.20-7.45 (m, 5H), 7.15 (d, 1H), 3.26-3.40 (m, 4H), 3.10-3.20 (m, 4H), 2.5 (s, 3H), 1.38 (s, 9H). ' INTERMEDIATE 13 4-[7-(2-r-butyl-phenylsulfenyl)-isoqHinoliii-l-yl]-piperaane-l-carboxyIic acidferf-butyl ester A mixture of 4-(7-bromo-isoquinoline-l-yl)-piperazuie-l-carboxylic acid, (err-butyl ester (0.5 g, 1.3 mmol), 2-r-butyl-tbiophenol (0.216 g, 1.3 mmol), Naf-BuO (0.44 g, 4.5 mmol), ! Pd(PPh3)4 (74 mg, 0.065 mmol) in n-BuOH (10 mL) was heated at 110 QC, 3h. The reaction mixture was filtered. The filtrate was concentrated and the residue was dissolved in ethyl acetate. The organic phase was washed wife water (50 mL x 3), separated and dried (MgS04), filtered. The volatiles were evaporated and the residue was purified by flash column chromatography (Si02, n-heptane: ethyl acetate 8:2) to give 440 mg of the ) title compound as colorless oil (yield 71 %). !H NMR (CDC13) 8 8.00-8.10 (m, 2H), 7.15- 7.65 (m, 7H), 3.60-3.70 (m, 1H), 3.30-3.45 (m, 4H), 3.05-3.20 (m, 3H), 1.55 (s, 9H), 1.50 (s,9H). INTERMEDIATE 14 4-j7-(3,4-IMcliloro-phenylsalfanyl)-isoqiiinollii-l-yl]-piperazine-l-carboxylic acid tert-butyl ester A mixture of4-(7-hromo-isoquinoline-l-yl)-piperazine-l-carboxylic acid, tert-butyl ester (0.5 g, 1.3 mmol), 3,4-dichloro-tbJopheiiol (165 uL, 1.3 mmol), NaiBuO (0.44 g, 4.5 mmol), Pd(PPh3)4 (74 mg, 0.065 mmol) in n-BuOH (10 mL) was heated at 110 °C, 3h. The reaction mixture was filtered. The filtrate was concentrated and the residue was dissolved in etiiyl acetate. The organic phase was washed with water (50 mL x 3), separated and dried (MgSCM), filtered. The volatiles were evaporated and the residue was purified by fiash column chromatography (Si02, n-pentane:ethyl acetate 9.5:0.5-*S:2) to give 230 mg of the title compound as colorless oil (yield 36 %). 'H NMR (CDCI3) 8 8.10-8.20 (m, 2H), 7.90 (bs, 1H), 7.65-7.75 (m, 2H), 7.10-7.55 (m, 3H), 3.50-3.65 (m, 4H), 3.20-3.30 (m, 4H), 1.50 (s, 9H). INTERMEDIATE 15 4-[7-(3,4-DimefliyI-phenylsnlfanyI)-isoqninoliii-l-yI]-piperazme-l-carboxylicacidtei«-butyl ester A mixture of 4-(7-bromo-isoquinoline-] -y])-niperazbe-l-carboxylic acid, tert-batyi ester (0,5 g, 1.3 mmol), 3,4-dimethyl-thiophenol (175 uL, 1.3 mmol), NafBuO (0.44 g, 4.5 mmol), Pd(PP&i)4 (74 mg, 0.065 mmol) in n-BuOH (10 mL) was heated at 110 °C, 3h. The reaction mixture was filtered. The filtrate was concentrated and the residue was dissolved in ethyi acetate. The organic phase was washed with wafer (50 mL x 3), separated and dried (MgSOO, filtered. The volatiles were evaporated and the residue was purified by flash column chromatography (Si02, n-pentane:ethyl acetate 9.5:0.5~»8:2) to give 260 mg of the title compound as colorless oil (yield 44 %). ]H NMR (CDCI3) 6 8.00-8.10 (m, 2H), 7.55-7.65 (m, 3H), 7.40-7.50 (m, 1H), 7.10-7.30 (m, 2H), 3.30-3.40 (m, 4H), 3.10-3.20 (m, 4H), 2.30 (s, 3H), 2.25 (s, 3H), 1.50 (s, 9H). INTERMEDIATE 16 4-[7-(3,5-Dimethy]-phenyIsulfanyI)-isoqiiinoliii-l-yI]-piperaziii6-l-carboxylicacidter/-butyl ester A mixture of 4-(7-bromo-isoquiaoIine-l-yl)-piperazine-l-caiboxyiic acid, tert-buty\ ester (0.5 g, 1.3 mmol), 3,5-dimethyl-thiophenol (ISO mg, 1.3 mmol),NalBuO (0.44 g, 4.5 mmol), Pd(PPfa3)4 (74 mg, 0.065 mmol) in aBuOH (10 mL) was heated at 110 °C, 3h. The reaction mixture was filtered. The filtrate was concentrated and the residue was dissolved in ethyl acetate. The organic phase was washed with water (50 mL x 3), separated and dried (MgSO*), filtered. The volatiles were evaporated and the residue was purified by ' flash column chromatography (S1O2, n-pentane: ethyl acetate 9.8:0.2-»8:2) to give 3S0 mg of the title compound as colourless oil (yield 65 %). 'H NMR (CDC13) 5 8.05-8,10 (m, 1H), 7.80-7.85 (m. 1H), 7.60-7.75 (m, 1H), 7.17-7,25 (m, 1H), 7.10 (bs, 2H), 7.00 (bs, 1H), 3.40-3.50 (m, 4H), 3.10-3.20 (m, 4H), 2.25 (bs, 6H), 1.50 (s, 9H). INTERMEDIATE 17 4-[7-(p-Cbloro-phenylsalfany^isoqninolin-l-ylj-piperaziiie-l-carboxylic acid tert-butyl ester A mixture of 4-(7-bromo-isoquinoline-l-yl)-piperazme-l-carboxylic acid, tert-butyl ester (0.5 g, 1.3mmol),^-chloro-thiophenol(188mg, 1.3 mmol), NafBuO (0.44 g, 4.5 mmol), Pd(PPh3)4 (74 mg, 0.065 mmol) in nEuOH (10 mL) was heated at 110 °C, 3h. The reaction mixture was filtered. The filtrate was concentrated and the residue was dissolved in ethyl acetate. The organic phase was washed wife water (50 mL x 3), separated and dried (MgS04), filtered. The volatiles were evaporated and the residue was purified by flash column chromatography (SiCb, n-pentane:ethy! acetate 9.5:0.5 -*■ 8:2) to give 300 mg of the title compound as colourless oil (yield 50 %). 'HNMR (CDCI3) 8 8.05-8.15 (in, 2H), 7.60-7.70 (m, 2H), 7.40-7.50 (m, 2H), 7.15-7.30 (m, 3H), 3.45-3.55 (m, 4H), 3.10-3.15 (m, 4H), 1.50(3, 9H). INTERMEDIATE 18 4-(7-PhenyIsulfanyMsoquinoline-l-yI)-piperazine-I-carboKylic acid, tert-butyl ester LCMS: 422,423. INTERMEDIATE 19 4-[7 LCMS: 478,479. ' INTERMEDIATE 20 4-(7-Phenylsutfanyl-isoqniiioIine-I-yl)-[l,4]diazepane-l-carboxyIic add, tert-butyl ester MS: 368,369,370. INTERMEDIATE 21 4-17-(4-rert-Buryl-phenyIsnIfanyl)-isoqninoIuie-l-yl]-[l,4Idiazepane-l-carboxyIicacid, ferf-bntyl ester MS: 424,425,426. ' INTERMEDIATE 22 4-[7-(2-Chloro-6-methyl-phenylsnlfanyl>-isoquinoline-l-yl]-El,4]diazepane-l-carboxylic acid, tert-butyl ester MS: 416,417,418. INTERMEDIATE 23 4-l7-(3,4-DimethyI-phenylsalfanyI)-isoqii!iio]bie-l-yIJ-[l,4Idiazepane-l-carboxylic acid, tert-butyl ester MS: 396,397,398. ■ INTERMEDIATE 24 4-I7-(3,4-DichIoro-pheDy!siitfanyl)-boqiiinoline-l-yl]-[l,4]diazepaiie-l-carbosyIic acid, tert-butyl ester MS: 436,437438. INTERMEDIATE 25 4-t7-(4-ChIoro-phenyIsulfanyl)-isoquinoline-l-yl]-[l,4Idiazepane-l-carboxy]icacid, rert-butyl ester MS: 402,404. INTERMEDIATE 26 4-[7-(3,4-Dimethyl-phenylsDifanyl)-isoqiiinoline-l-yll-[ly4]diazepaiie-l-carljoxylic acid, fert-butyl ester LCMS: 464,465,466. INTERMEDIATE 27 4-17-(2-tert-BatyI-phenyIsulfanyI)-isoquinoline-l-ylI-El,4]diazepaBe-l-carboxyIicadd, tert-butyl ester LCMS: 492,493,494. BOC deprotection and oxidation of thiols to sulphone derivatives Each thiol (0.2-1.14 nnnol) was dissolved in trifluoroacetic acid (1.5 mL) at 0 °C and stirred for 15 mina at this temperature. To this was added 33% aqueous hydrogen peroxide solution (5-100 mL). The resulting mixture was stirred at room temperature for 90 min and then treated with sodium hydroxide solution (1M, 25 mL). Extraction of this mixture with ethyl acetate (3x50 mL) was followed by the washing of the combined organic layers with brine (50mL). The organic extracts were dried over anhydrous sodium sulfate and then the solvent was removed under reduced pressure. The crude product was purified by preparative LCMS. Treatment of the purified material with HCl/Ether (1M, 1 mL) gave the final product as a white solid. EXAMPLE 16 7-(2-Chloro-6-methyl-benzeiiesa!fonyl>l-piperazin-l-yI-isoqiiinoline hydrochloride Amixtureof4-[7-(2-chloro^-memyl-phenyIsulfanyl)-isoqTimolm-l-yl]-pip carboxyiic acid tert-butyl ester (160 mg, 0.340 mmol), H2Oz (30% in water, 200 uL), trifhioroacetic acid (2 mL) was heated at 50 "C, 2h. A water solution of NaOH (IN) was added (pH = 14), ethyl acetate was added and the organic phase was separated, dried (MgSO-O, filtered. The fillrated was concentrated and the residue was purified by flash column chromatography (SiCh, dicWoronre&arie:meaianaI 8:2) to lead to 77 mg of the product compound as free base (yield 56 %). The free base was converted into hydrochloride by treatment with EC1 in diethyl ether. *H NMR (CH3OH- EXAMPLE 17 7-(2-^-Bulyl-benzenesnlfonyI)-l-piperazin-l-yI-isoqHniol!ne hydrochloride A mixture of 4-[7-(2-/butyl-phenylsulfanyl)-isc«5uinoto-l-yl]-piperazirie-l-carboxylic acid terf-bulyl ester (273 mg, 0.571 mmol), H2Oz (30% in water, 1 mL), trifhioroacetic acid (3 mL) was heated at 50 °C, 2h. The reaction was continued overnight at 35 °C. A water solution of NaOH (IN) was added (pH = 14), ethyl acetate was added and the organic phase was separated, dried (MgSQO, filtered. The filtrated was concentrated and the residue was purified by flash column chromatography (SiO?, dichloromethane:methanol 8:2) to lead to 50 mg of the title compound as free base (yield 56 %). The free base was converted into hydrochloride by treatment with HC1 in diethyl ether. *H NMR (CHsOH-dj) 5 8.55 (d, 1H), 8.25 (d, 1H), 7.95-8.10 (m, 3H), 7.55 (d, 1H), 7.55-7.65 (m, 2H), 7.4 (d, 1H), 3.60-3.75 (m, 4H), 3.40-3.50 (m, 4H), 1.55 (s, 9H). EXAMPLE 18 7-(3,4-Dicfaloro-benzenesulfonyI)-l-piperadn-l-yI-isoquinoline hydrochloride A mixture of 4-[7-(3j4-dichloro-phenylsulianyl)-isoquino]m-l-yl]-piperazhie-l-carboxyHc acid tert~butyl ester (230 mg, 0.47 mmol), H2O2 (30% in water, 0,5 mL), irifluoroacetic acid (1.5 mL) was heated at 50 °C, 2h. The reaction was continued overnight at 35 °C. A water solution of NaOH (IN) was added (pH = 14), ethyl acetate was added and the organic phase was separated, dried (MgSO^), filtered. The filtrated was concentrated and the residue was purified by flash column chromatography (Si02, dichloromethane:methanol 9:1) The free base was converted into hydrochloride by treatment with HC1 in diethyl ether to obtained 45 mg of the title compound. *H NMR. (CH3OH-d4) 8 S.75-8.85 (m, IH), 8.10-8.30 (m, 4H), 7.90-8.00 (m, IH), 7,75-7.85 (m, 1H), 7.50-7.60 (m, IH), 3.85-3.90 (m, 4H), 3.50-3.70 (m, 4H). EXAMPLE 19 7-(3,4-Dtmethyl-benz«iesulfooyl)-l-piperaziB-I-yi-isoquiooIme hydrochloride Amixtureof4-[7-(3,4-dimethyl-phenylsulfanyl)-isoqumolm-l-yl]-pipera2ine-l-carboxyhc acid tert-butyl ester (260 mg, 0.58 mmol), H202 (30% in water, 0.5 mL), trifluoroacetic acid (1.5 mL) was heated at 50 °C, 2h. The reaction was continued overnight at 35 °C. A water solution of NaOH (IN) was added (pH = 14), ethyl acetate was added and the organic phase was separated, dried (MgSO*), filtered. The filtrated was concentrated and the residue was purified by flash column chromatography (SiO:, dichioromethane:methanol 9:1) The free base was converted into hydrochloride by treatment with HC1 in diethyl ether to obtained 20 mg of the title compound. *H NMR (CH3OH-^) 6 8.75-8.80 (m, IH), 8.10-8.25 (m, 3H), 7.70-7.85 (m, 2H), 7.60-7.70 (m, IH), 7.35-7.40 (m, IH), 3.90-4.00 (m, 4H), 3.55-3.65 (m, 4H), 2.35 (bs, 6H). EXAMPLE 20 7-(2^-Diraethyl-benzenesulfoayO-l-piperazin-l-yl-isoq,uinoIiae hydrochloride A mixture of 4-[7-(2,5-dimemyl-nhenyl5ulfanyl)-isoqum acid *ew-butyl ester (380 mg, 0.846 mmol), H2O2 (30% in water, 0.5 mL), trifluoroacetic acid (3 mL) was heated at 50 °C, Zh. The reaction was continued overnight at 35 °C. A water solution of NaOH (IN) was added (pH = 14), ethyl acetate was added and the organic phase was separated, dried (MgS04), filtered. The filtrated was concentrated and the residue was purified by flash column chromatography (Si02, dicMoTOmethane:methanol 9.8:0.2->9.5:0.5) The free base was converted into hydrochloride by treatment with HC1 in diethyl ether to obtained 120 mg of the title compound. 'H NMR (CH3OH-^) 8 8.75-8.80 (m, IH), 8.25-8.30 (m, IH), 8.05-8.20 (m, 2H), 7.60-7.70 (m, 3H), 7.30-7.35 (m, IH), 4.00-4.10 (m, 4H), 3.60-3.70 (m, 4H), 2.30-1.35 (bs, 6H). EXAMPLE 21 7-(p-CMoro-benzenesuIfooyO-l-piperazin-l-yMsoquinoIJneIiyi}roctiIoride A mixture of 4-[7-(p-chloro^heQylsulf^yl)-isoquino!in-l-yl]-piperazine-l-carboxylic acid /erf-butyl ester (297 mg, 0.65 mmoJ), H2Q; (30% in water, 0.5 mL), trifluoroacetic acid {3 mL) was heated at 50 DC, 2k The reaction was continued overnight at 35 CC. A water solution of NaOH (IN) was added (pH = 14), ethyl acetate was added and the organic phase was separated, dried (MgSCU), filtered. The filtrated was concentrated and the residue was purified by flash column chromatography (SiCh, dichloromethanermefhanol 9.5:0.5->9.0:1.0) The free base was converted into hydrochloride by treatment with HC1 in diethyl ether to obtained 70 mg of the title compound. 'H NMR (OfcOH-^) 8 8.75-8.85 (m, 2H), 8.10-8.25 (m, 3H), 8.00-8.08 (m, 2H), 7.60-7.68 (m, 3H), 3.85-3.95 (m, 4H), 3.55-3.65 (m, 4H). EXAMPLE 22 7-BeH2enesiilfonyl-3-[1,4Jdiazepaa-l-yJ-isoquiBolinebydrocbloride 30 mg. 5H NMR (DMSO-dfl) 5 9.3 (s, 1 H), 8.58 (s, 1 H), 8.26-8.30 (d, J= 9 Hz, 1 H), 8.1-8.13 (ra, 2 H), 8.01-8.06 (d, J= 6 Hz, 1 H), 7.6-7.76 (m, 3 H), 7.53-7.58 (d, J= 6 Hz, 1 H), 3.70-3.90 (m, 4H) 3.58-3.66 (m, 2 H), 3.29-3.40 (m, 2H); LCMS: 368,369 HPLC: 98 %. EXAMPLE 23 7-(4-tert-ButyI-benzenesnlfonyl)-l-[l,4]diazepan-l-yI]-isoqiiinoIme hydrochloride Isolated 69 mg. 'HNMR(DMSO-dtf) 6 9.2 (s, 1 H), 8.65 (s, 1 HO, 8.09-8.15 (d,/= 6Hz, 1 H), 8.03-8.08 (d, J= 15 Hz, 1 H), 7.89-7.96 (d, /= 9 Hz, 2 H), 7.60-7.67 (d, J= 9 Hz, 2 H), 7.33-7.38 (d, /= 9 Hz, 1 H), 4.01-4.09 (m, 2 H), 3.83-3.91 (m, 2 H), 3.43-352 (m, 2 H), 3.23-3.33 (m, 2 H), 1.25 (s, 9 H); LCMS: 424,425, HPLC: 97 %. EXAMPLE 24 7-(2-Chforo-6-methyl-benzenesulfonyl)-l-[l,4]diazepan-l-yl]-isoqumoline hydrochloride ] Isolated 27 mg 'H NMR (DMSO-d6) 8 8.81 (s, 1 H), 8.28 (m, 1 H), 8.10-8.18 (d, J= 6 Hz, 1 H), 7.94-8.08 (m, 2 H), 7.45-7.62 (m, 3 H), 7.36-7.42 (d, 7= 6 Hz, 1 H), 3.75-3.86 (m, 2 H), 3.41-3.51 (m, 2 H), 3.18-3.32 (m, 2 H), 2.86 (s, 3 H), 2.14-2.19(m 2 H); LCMS: 416,418 HPLC: 98%. EXAMPLE 25 7-{3j5-Diiiiefliyl-benzenesiiIfonyl)-l-[l,4]diazepan-l-yI]-isoqoiDoline hydrochloride Isolated 62 mg. 'HNMR (DMSO-4;) 8 9.35 (s, 1 H), 8.67 (m, 1 H), 8.00-8.18 (m, 3 H), 7.58-7.69 (m, 2 H), 7.45-7.41 (d, J= 6 Hz, 1 H), 7.30-7.35 (m, 1 H), 4.06-4.14 (m, 2 H), 3.S6-3.97 (m, 2H), 3.42-3.52(m,2H), 3.23-3.31 (m, 2H), 2.33 (s,6H)2.23-2.25 (m2 H); LCMS: 436,438, HPLC: 95 %. EXAMPLE 26 7-(3,4-Dichloro-beiizeflesuUbii>1>-l-[l,4]diazepaD-l-ylJ-isoqiiraoline, hydrochloride Isolated 11 mg. ]H NMR (CD3OD) 5 8.88 (m, 1 H), 8.23-8.29 (d, J= I2Hz, 1 H), 8.13-8,16 (d, J= 3 Hz, 1 H), 8.04-8.10 (d, /= 9 Hz, 1 H), 7.88-7.94 (d, /= 9 Hz, 1 H), 7.79-7.84 (d,^=6Hz,lH), 7.67-7.73 (d, J = 9 Hz, 1 H), 7.42-7.46 (d, J=6Hz,lH), 4.28-4.35 (m, 2 H), 4.09^.16 (m, 2 H), 3.69-3.75 (m, 2 H), 2.33-2.46 (m, 2 H); LCMS: 368,369; HPLC: 97 %. EXAMPLE 27 7-(4-ChlorfrbeBzenesa!fony^-l-ll,4]disaepaB-l-yl]-i8oquiBolme)b-ydrocliIoride Isolated 41 mg. 'H NMR (DMSO-4) 5 9.27 (s, 1 H), 8.68 (m, 1 H), 7.99-8.17 (m, 5 H), 7.66-7.75 (d, /= 9 Hz, 2 H), 7.33-7.39 (d, J~ 6 Hz, 1 H), 4.03-4.11 (m, 2 H), 3,83-3.93 (m, 2 H), 3.43-3.53 (m, 2 H), 3.23-3.32 EXAMPLE 28 7-(3,4-Dimethyl-beazeoesulfony])-l-Il,4]diazepao-l-yl]-iSoqiiinoliiie, hydrochloride Isolated 10 mg. 'H NMR (DMSO-tfc) 5 9.41 (s, 1 H), 8.67 (s, 1 H), 8.00-8.16 (m, 3 H), 7.76-7.82 (m, 1 H), 7.68-7.77 (d, /= 9 Hz, 1 H), 7.32-7.42 (d, J= 9 Hz, 2 H), 3.99-4.40 (m, 4 H), 3.49 (m, 2 H), 3.33 (m, 2 H), 2.29 (s, 3 H), 2.25 (s, 3 H); LCMS: 396,397; HPLC: 92 %. EXAMPLE 29 7^2-rert-Butyl-benzenesnlfMi5l)-l-[l,4]diazepao-l-y!]-isoqninoline, hydrochloride Isolated 5 mg. *H NMR (DMSO-&) S 9.27 (s, 1H), 8.52 , 7.72-7.78 (m, 1 H), 7.61-7.70 (m, 1 H), 7.40-7.45 (d, J= 9 Hz, 2 H), 3.69-3.99 (m, 4H),3.43 (s,2H), 3.25 (s,2H),2.G5-2.26(m,2H);1.S2(s, 9 H);LCMS: 424,425; HPLC: 90 %. EXAMPLE 30 7-BenzenesnlfonyI-l-piperazin-yi-isoqninoIine, hydrochloride Isolated 10 mg. lH NMR PMSO-rf*) 8 9.04 (s, 1 H), 8.65 (s, 1 H), 8.12-8.16 (d, J= 6 Hz, 1 H), 7.98-8.05 (m, 5 H), 7.58-7.72 (m, 2 H), 7.32-7.36 (d, 7= 6 Hz, 1 H), 3.98-4.04 (m, 4 H), 3.S0-3.86 (in, 4 H); LCMS: 354,355; HPLC; 98 %. EXAMPLE 33 7-(4-tert-Bnty!-beiizenesaJfonyl-l"piperaziii-yI-isoqiunoIuie, hydrochloride Isolated 10 mg. *HNMR (DMSO-d6) 5 9.33 (s, 1H), 8.57 (s, 1 H), 8.24-859 (d, J= 9 Hz, 1 H), 8.11 (m, 2 H), 7.91-7.97 (d, J= 9 Hz, 2 H), 7.60-7.66 (d, /= 12 Hz, 2 H), 7.52-7.57 Cd,/= 6 Hz, 1 H), 3.59-3.68 Cm, 4 H), 3.29-3.40 (m, 4 H), 1.24 Cs, 9 H); LCMS: 410,411 HPLC: 90 %. General method C Mitsonotm reaction of 4-nitro-l-naphthol with boc-protected 3-hydroxypyrrolidine and 4-hydroxypiperidine 4-Nitro-l-naphfliol (1 equiv.) was dissolved in THF (3 mL/mmol), tert-butyl 3-hyaYoxypyrrolidrae-l-carboxylate (2 equiv.) was added followed by PPhs (2 equiv.). The solution was kept under N2-atmosphere and cooled with ice-bath. Diethylazodicarboxylate (DEAD; 2 equiv.) was added dropwise. The ice-balh was removed after 10 min and the reaction mixture was stirred at ambient temperature overnight. The solvent was evaporated and the residue was re-dissolved in EtOAc. The formed precipitate was collected by filtration. The solution was concentrated in vacuo and purified by flash chromatography (Si02, EtOAc:zso-hexane 2:8-»EtOAc) General method D Redaction of nitronaphthalene derivatives To a solution of corresponding nitronaphthalenes (1 equiv.) (prepared by General method A) in MeOH (2 rruVrnmol), was added Pd/C (10%) and the reaction mixture was stirred overnight under hydrogen (I aim). The reaction mixture was filtered and the filtrate was concentrated in vacuo to give corresponding aminonaphfhalene derivatives. General method E Reaction of arainoBaphthalene derivatives with sulfonyl chlorides To a solution of the aminonaphthatene derivatives (1 equiv,) in CH2CI2 (8 rnL/mmol) was added pyridine (3 equiv.) followed by the corresponding sulfonyl chloride (1.2 equiv.). The mixtures were stirred at ambient temperature overnight, washed with HC1 (1M) (2 mL) and dried (MgS04). The volatiles were eliminated under vacuo and gave the crude product which were purified by flash chromatography (SiC>2, EtOAc:iso-hexane 1:4) to give desired sulfonamide. General method F Deprotection of boc-gronp The sulfonamide derivatives (prepared by Genera] Method Q were dissolved in a small amount of MeOH and treated with an excess of HC1 in diethyl ether (1M>. Stirring at ambient temperature overnight resulted in a precipitate which were collected by filtration giving the title compounds as its hydrochloride salts. General method G 3-Hydroxypyrrolidine (lequiv.) was dissolved in MeOH (lmL/mmol) and cooled on ice-bath. (BOC)30 (1.lequiv.) was added and me mixture was stirred for 2 h at ambient temperature. Pyridine/water (10/lOmL) was added and the mixture was stirred overnight. Evaporation of solvents and co-evaporation with toluene provided the desired boc-protected 3-hydroxypyrrolidine. 5ppm 1.48 (a, 9 H) 1.99 (m, 4H)3.54 (m, 2H) 3.70 (m, 2H) 4.87 (m, 1H) 6.82 (d, >9.04 Hz, 1 H) 7.59 (m, 1H) 7.74 (m, 1 H) 8.38 (d, 7=8.53 Hz, 2 H) 8.77 (d, 7=8.53 Hz, 1H). MS (BSI+) for CwHa^Os Wz 373.0 (M+H)+, 390.2 (M+NRtf, 317.0 (M-lBu)+. HPLC 98%, RT=2.973 min (SystemBl, 10-90% MeCN over 3 min). INTERMEDIATE 34 (ert-Butyl 4-[(4^amino-l-naphthyl)oxyJpiperidiiie-l-carboxylate (General Method C) The compound was prepared from intermediate 6 (2.3 g, 7.0 mmol), Yield: 2g (95%) as pick oil HPLC 94%, Ri=2.885 min (System Bl, 10-90% MeCN over 3 min). !H NMR (400 MHz, CDCt3) 8 ppm 1.46 (s, 9 H) 1.80-1,98 (m, 4 H) 3.35-3.41 (m, 2 H) 3.46 (s, 3 H) 3.69-3.75 (m, 2 H) 3.88 (br s, 1 H) 4.50-4.54 (m, 1 H) 7.45-7.50 (m, 2 H) 7.79-7.81 (m, 1 H) 8.22-8.24 (m, 1 H). MS (ESI+) for C20H26N2O3 m/z 343.2 (M+H)+. HPLC 94%, Rr=2.735 min (System Al, 10-97% MeCN over 3 min). INTERMEDIATE 35 (ert-Butyl4-[(4-{{(4-chlorophenyl)sulfonyl]a!iiuio}-l-iiaplithyI)osy]pJperidine-l-carboxylate (General method E) The compound was prepared from intermediate 7 (0.25 g, 0.73 mmol), Yield: 0.29g (77%)-HPLC 98%, Ri=2.906 min (System Al, 10-97% MeCN over 3 min). !H NMR (400 MHz, CDC13) 6 ppm 1.47 (s, 9 H) 1.88 (m, 2 H) 1.98 (m, 2 H) 3.47 (m, 2 H) 3.68 (m, 2 H) 4.69 (m, 1 H) 6.61 (s, 1 H) 6.70 (d, 7=8.03 Hz, 1 H) 7.17 (d, 7=8.03 Hz, 1 H) 7.32 (m, 2 H) 7.43 (m, 2 H) 7.62 (m, 2 H) 7.70 (m, 1 H). MS (ESI+) for C26H29CIN2O5S m/z 534.0 (M+NH*/, 461.2 (M-tBuf. HPLC 98%, RT=2.843 min (System Bl, 10-90% MeCN over 3 min). INTERMEDIATE 36 tert-BBtyl4-K4-{[(4-methoK^lieny!)su]fonyI]ammo}-l-naphthyI)oxy]piperidme-l- carboxyiaie (General methodE) The compound was prepared from intermediate 7 (0.25 g, 0.73 mmol). Yield: 0.21g (56%) of (he title compound as pink solid. HPLC 100%, Rr=2.755 min (System Al, 10-97% MeCN over 3 min). !H NMR (400 MHz, CDC13) 8 ppm 1.47 (s, 9 H) 1.86-2.01 (m, 4 H) 3.43-3.49 (m, 2 H) 3.65-3.71 (m, 2 H) 3.79 (s, 3 H) 4.65-4.70 (m, 1 H) 6.58 (s, 1 H) 6.69 (d, >8.53 Hz, 1 H) 6.83-6.79 (m, 2 H) 7.17 (d, >8.03 Hz, 1 H) 7.39-7.44 (m, 2 H) 7.61-7.64 (m, 2 H) 7.75-7.77 (m, 1 H) 8.21-8,24 (m, 1 H). MS (ESI+) for Mas^O^S m/2 530.2 (M+NH4)", 457.2 (M-fBu)+, 413.4 (M-Bocf. HPLC 99%, R-i=2.668 min (System Bl, 10-90% MeCNover 3 min). INTERMEDIATE 37 tert-Butyl4-[(4-{[(5-flnoro-2-methylphenyl)siilfonyl]aniino}-l-naphthyl)oxy]piperidrae-l-carboxylate (General method E) The compound was prepared from fert-butyl 4-[(4-amino-l-naphtiiyl)oxy]pipeiidine-l-carboxylate (0.25 g, 0.73 mmol). Yield: 0.24 g (64 %) of the title compound as a pink solid. HPLC 99 %, RT=2.809 min (System Bl, 10-90% MeCN over 3 min). !H NMR (400 MHz, CDCI3) S ppm 1.46 (s, 9 H) 1.83-1.98 (m, 4 H) 2.54 (s, 3 H) 3.42-3.48 (m, 2 H) 3.63-3.69 (m, 2 H) 4.644.68 (m, 1 H) 6.64-6.68 (m, 2 H) 7.03 (d, J=8.53 Hz, 1H) 7.10 (m, 1 H) 7.22 (dd, J=8.53, 5.02 Hz, 1 H) 7.44-7.48 (m, 2 H) 7.55 (dd, J=8.53,2.51 Hz, 1 H) 7.83-7.86 (m, 1H) 8.24 (m, 1 H). MS (ESI+) for C;7H3,FN205S m/z 532.2 (M+NH*)+, 459.2 (M-iBu)+, 415.2 (M-Boc)+. HPLC 100 %, RT^.877 min (System Al, 10-97% MeCN over 3 min). INTERMEDIATE 38 fert-Bntyl4-[(4-{[(5-chloro-2-thienyI)sulfonyl]amino}-l-naphthy!)oxy]piperidiae-l-carboxylate (General method E) The compound was prepared from tert-butyl 4-[(4-amino-l-naphmyl)oxy]piperidine-l-carboxylate (0.25g, 0.73mmol). Yield: 0.25 g (65 %) of the title compound as a pink solid. HPLC 98 %, Rr=2.827 min (System Bl, 10-90% MeCN over 3 min). 'HNMR (400 MHz, CDCI3) S ppm 1.47 (s, 9 H) 1.86-2.03 (m, 4 H) 3.45-3.51 (m, 2 H) 3.66-3.72 (m, 2 H) 4.69-4.74 (m, 1 H) 6.66 (s, 1 H) 6.74-6.76 (m, 2 H) 7.14 (d, J^4.02 Hz, 1 H) 7.30 (d, J=8.03 Hz, 1 H) 7.45-7.50 (m, 2 H) 7.76-7.79 (m, 1ff) 8.25-8.28 (m, 1 H) MS (ESI+) for C24H27CIN2O5S2 m/z 540.4 (M+NH4)* 467.2 (M-tBu)+. HPLC 99 %, RT=2.910 min (SystemAl, 10-97 % MeCN over 3 min). INTERMEDIATE 39 ferf-Butyl (3R)-3-hydroxypyrroIidiae-l-carboxylafe (General method G) The compound was prepared from (3R)-3-hydroxypyrroIidine (5 g, 57.4 mmol). Yield: 9.6 g (90 %) of the title compound !H NMR (400 MHz, CDCb) 5 ppm 1.43 (s, 9 H) 1.90-1.98 (m, 2 H) 3.27-3.47 (m, 4H) 4.40 (br s, 1H). INTERMEDIATE 40 ierf-Butyl (3S)-3-hydroxypyrrolidiiie-l-carboxyIate (General method G) The compound was prepared from (3S)-3-hydroxypyrrolidine (5 g, 57.4 mmol). Yield: 8 g (86 %) of the title compound. 'H NMR (400 MHz, CDC13) S ppm 1.40 (s, 9 H) 1.86-1.91 (m, 2 H) 3.24-3.42 (m, 4H) 4.36 (br s, 1H). INTERMEDIATE 41 (ert-Butyl (3S)-3-[(4-nitro-l-naphtiiyI)oxy]pyrroIidine-l-carboxylate (General method Q The compound was prepared from tert-butyl (3R)-3-hydroxypyrroIidine-l-carboxylate (3.56 g, 19 mmol) and4-nitro-l-naphthol (3 g, 15.9 minol). Yield: 5 g (88 %) of the title compound as yellow oil. ]H NMR (400 MHz, CDC13) S ppm 1.45 (d, J=7.03 Hz, 9 H) 2.22-2.38 (m, 2 H) 3.54-3.83 (m, 4 H) 5.18 (br s, 1 H) 6.74 (d, J=8.53 Hz, 1 H) 7.56 (t, 3=7.78 Hz, 1 H) 7.71 (t, J=7.78 Hz, 1 H) 8.29 (d, J=8.53 Hz, 1 H) 8.33 (d, J=8.53 Hz31 H) 8.72 (d, J=8.53 Hz, 1 H). MS (ESI+) for C19H23N2O5 m/z 376.2 (M+NH*)*, 303.2 (M- tBu)+. HPLC 100 %? RT=2.768 min (System Al, 10-97% MeCN over 3 min). INTERMEDIATE 42 terf-Bntyl (3R)-3-[(4-nitro-l-Daphthyl)oxy]pyrrolidiiie-l-carboxyIate (General method Q The compound was prepared from ten -butyl (3S)-3-hydroxypyrrolidrne-l-carboxylate (3.56 g, 19 mmol) and 4-nitro-l-napn1hoI (3 g, 15.9 mmol). Yield: 2.8 g (49 %) of the title compound as yellow oil. !H NMR (400 MHz, CDC13) 5 ppm 1.46 (d, J=7.03 Hz, 9 H) 2.26-2.38 (m, 2 H) 3.55-3.81 (tn, 4 H) 5.20 (br s, 1 H) 6.77 (d, J=8.53 Hz, 1 H) 7.59 (t, J=7.53 Hz, 1 H) 7.72-7.76 (m, 1 H) 8.32 (d, J=8.03 Hz, 1 H) 8.37 (d, J=8.53 Hz, 1 H) 8.76 (d, J=8.53 Hz, 1 H). HPLC 95 %, Ri=2.775 min (System Al, 10-97 % MeCN over 3 min). INTERMEDIATE 43 tert-Butyl (3S>H(4-anuno-l-naphthyl)oxy]pyrrolidrae-l-carboxylate (General method r>) The compound was prepared torn ?ert -butyl (3S)-3-[{4-mtro-l-naphthyl)oxy]pyrrolidine-1-carboxylase (5 g, 14 mmol). Yield: 3.5 g(76 %)ofthe title compound as dark pink solid. 'HNMR (400 MHz, CDCI3) 6 ppm 1.46 (d, J=14.56 Hz, 9 H) 2.08-2.13 (m, 1 H) 2.27-2.30 (m, J=13.05 Hz, 1 H) 3.54-3.77 (m, 4 H) 3.88 (br s, 2 H) 4.96 (br s, 1 H) 6,65-6.70 (m, 2 H) 7.45-7.51 (m, 2 H) 7.79-7.81 (m, 1 H) 8.15-8.19 (ra, 1H). MS (ESI+) for C39H24N2O3 m/z 329.2 (M+H)+, 273.2 (M-tBu)+, 229.2 (M-Boc)+. HPLC 95 %, RTM.854 min (System Al, 10-97 % MeCN over 3 min). INTERMEDIATE 44 tert-Butyl (3R)-3-[(4-ammo-l-Haplithyl)oxy}pyiToIidine-l-carboxylate (General method D) The compound was prepared from ierf -butyl (3R)-3-[(4-nitro-l-n3phthyl)oxy]pyrrolidine-1-carboxylate (2.8 g, 7.8 mmol). Yield: 1.8 g (72 %) of the title compound as dark pink 1 solid. 'HNMR(400 MHz, CDCI3) 6ppm 1.46 (d, J=14.56Hz, 9H) 2.07-2.14 (m, 1 H) 2.27-2.30 (m, 1 H) 3.54-3.77 (m, 4 H) 3.93 (br s, 2 H) 4.96 (br s31 H) 6.65-6.70 (m, 2 H) 7.45-7.51 (m, 2 H) 7.79-7.81 (m, 1 H) 8.16-8.18 (m, 1H). MS (ESI+) for CISKMNJQB m/z 329.2 (M+H)+, 273.2 (M-tBu)+, 229.2 (M-Boc)+. HPLC 94 %, RT=1.751 min (System Al, 10-97% MeCN over 3 min). INTERMEDIATE 45 terNEHtyl(3S>3-[(4-{[(4-chlorophenyOsulfonyl]aminoJ-l-naphthyl)oxy]pyiTOIidine-l-carboxylate (General method E) The compound was prepared from fert-butyl (3S)-3-[(4-nitro-l-naphthyl)oxy]pyn;oIidine-) 1-carboxylate (0.3 g, 0.9mmol) and4-chloro-phenylsulfonylchloride (0.23 g, 1.1 mmol). Yield: 0.23 g (50 %) of the title compound. *H NMR (400 MHz, CDCk) 5 ppm 1.46 (d, J=4.52 Hz, 9 H) 2.15-2-34 (m, 2 H) 3.54-3.74 (m, 4 H) 5.05 (br s, 1H) 6.62-6.71 (m, 2 H) 7.17-7.23 (m, 1 H) 7.33 (d, J=8.53 Hz, 1 H) 7.39-7.43 (m, 2 H) 7.62-7.64 (m, 2 H) 7.65-7.70 (m, J=6.02 Hz, 1 H) 8.18 (d, J=8.53 Hz, 1H) MS (ESI+) for CisHnCI^OsS m/z 520.2 {M+NH4)+, 447.0 (M-tBu)\ HPLC 100 %, RT=2.772 min (System Al, 10-97 % MeCN over 3 min). INTERMEDIATE 46 tert-Bufyl(3R>3-[(4-{[(4-chlorophenyl)sulfoDyl]ammo}-l-Haphlhyl)oxy]pyiTOl«line-1-carboxylate (Genera! method E) The compound was prepared from tert-butyl (3R)-3-[(4-nitro-l-naphmyl)oxy]pyrrolidine-1-carboxylate (0.3 g, 0.9 mmol) and 4-chloro-phenylsulfonylchloride (0.23 g, 1.1 mmol). Yield: 0.4 g (87 %) of the title compound. TH NMR (400 MHz, CDC13) S ppm 1.46 (d, J=4.52 Hz, 9 H) 2.15-2-34 (m, 2 H) 3.54-3.74 (m, 4 H) 5.05 (br s, 1 H) 6.60-6.66 (m, 2 H) 7.17-7.23 (m, 1 H) 7.33 (d, J=8.53 Hz, 1 H) 7.39-7.43 (m, 2 HJ 7.62-7.64 (m, 2 H) 7.65-7.70 (m, J=6.02 Hz, 1 H) 8.18 (d, J=S.53 Hz, 1 H) MS (ESI+) for C^ClNzOsS m/z 520.2 (M+NH*)*, 447.0 (M-tBu)+. HPLC 100 %, RT=2.769 min (System Al, 10-97 % MeCN over 3 min). EXAMPLE 32 4-ChIoro-N-[4-(pyrrolidiii-3-yloxy)-l-Qaphthyl]beiizenesnlfonamide hydrochloride (General method F) The compound was prepared from intermediate 3 (0.13 g, 0.26 mmol). The solid was Hirther purified by trituration with diethyl ether giving 0.11 g (95%) of the title compound as white solid HPLC 98%, RT=1.810 min (System Al, 10-97% MeCN over 3 min). !H NMR (400 MHz, DMSO-d6) 6 ppm 2.21-2.26 (m, 2 H) 3.32-3.37 (m, 2 H) 3.48-3.50 (m, 2 H) 5.28 (br s, I H) 6.91-6.98 (m, 2 H) 7.44-7.50 (m, 2H) 7.56-7.64 (m, 4 H) 7.S8-7.90 (m, 1 H) 8.20-8.23 (m, 1 H). MS (ESI+) for C2oH,9ClN203S m/z 401.2 (M+H)+. HPLC 98%, RT=1.651 min (System Bl, 10-90% MeCN over 3 min). EXAMPLE 33 4-Methoxy-N-[4-(pyrroIidm-3-yloxy)-l-naphthyl]benzenKiilfonaniide hydrochloride (General method F) The compound was prepared from intermediate 4 (0.18 g, 0.36 mmol), Yield: 0.12 g (76%) ofrae title compound as awhite solid. HPLC 100%,RT=1.490mui(SystamBl, 10-90% MeCN over 3 min). 'H NMR (400 MHz, DMSO-d6) 8 ppm 2.20-2.25 (m, 2 H) 3.31-3.53 (m, 4 H) 3.78 (s, 3 H) 5.27 (br s, 1 H) 6.90-6.97 (m, 2 H) 7.00 (d, .7=8.53 Hz, 2 H) 7.43-7.48 (m, 2 H) 7.57 (d, J=8.53 Hz, 2 H) 7.93-7.96 (m, 1 H) 8.19-8.22 (m, I H) 9.63 (br s, 2 H). MS (ESI+) for C21H22N2O4S m/z 409.2 (M+H)+. HPLC 100%, R^l.639 rain (System Al, 10-97% MeCN over 3 min). EXAMPLE 34 S-Chloro-N-[4-(pyrrolidiB-3-yloxy>l-ndphthyl]thiopheiie-2-snlfonamide hydrochloride (General method F) The compound was prepared from intermediate 5 (0.20 g, 0.39 mmol), Yield: 0.14 g (80%) ofthe title compound as a pale white solid. HPLC 99%, RT=1-651 min (System Bl, 10-90% MeCN over 3 min). 'H NMR (400 MHz, DMSO-ds) 5 ppm 2.23-2.26 (m, 2 H) 3-28^ 3.39 (m, 2 H) 3.40-3.56 (m, 2 H) 5.32 (br s, 1 H) 6.99 (d, J=8.53 Hz, 1 H) 7.13 (d, .7=8.03 Hz, 1 H) 7.15 (d, J=4.02 Hz, 1 H) 7.26 (d, >4.02 Hz, 1 H) 7.48-7.52 (m, 2 H) 7.92 (dd, .7=6.53,3.01 Hz, 1 H) 8.25 (dd, 7=6.53,3.01 Hz, 1 H) 9.60 (s, 1 H). MS (ESI+) for CIBHITCINZO^S; mJz 409.2 (M+H)+. HPLC 99%, RT=1.818 min (System Al, 10-97% MeCN over 3 min). EXAMPLE 35 4-Chloro-N-[4-(pipcridiD-3-yloxy)-l-flaphthyI]beiizenesn!foDamide hydrochloride (General method F) The compound was prepared from intermediate 8 (0.26 g, 0.50 mmol), Yield: 0.12 g (53%) ofthe title compound as awhite solid. HPLC 100%, RT=1.872 min (System Al, 10-97% MeCN over 3 min). 'H NMR (400 MHz, DMSO-ds) 5 ppm 1.95-1.99 (m, 2 H) 2.14-2.19 (m, 2 H) 3.11 (br s3 2 H) 3.26 (br s, 2 H) 4.84 (br s, 1 H) 6.92-6.99 (m, 2 H) 7.44-7.51 (m, 2 H)7.57-7.65 (m,4H) 7.91 (d,7=7.53Hz, 1 H) 8.17(d,>7.03Hz, 1 H) 8.94(br s, 1 H) 9.05 (br s, 1H) 10.11 (s, 1H). MS (ESI+) for C2iH21CIN203S m/z 415.2 (M+H)+. HPLC 99%, RT=1.657 min (System Bl, 10-90% MeCN over 3 min). EXAMPLE 36 4-Methoxy-N-[4-(piperidiii-3-yloxy)-l-naphth)'l]beiizenesnlfonamide hydrochloride (General method F) The compound was prepared from intermediate 9 (0.19 g, 037 rmnol), Yield: 0.15 g (90%) of the title compound as a white solid. HPLC 97%, Ri=1.508 min (System Bl, 10-90% MeCN over 3 min). lH NMR (400 MHz, DMSO-d6) S ppm 1.96 (m, 2 H) 2.16 (m, 2 H) 3.10 (m, 2 H) 3.26 (m, /=6.02 Hz, 2 H) 3.78 (s, 3 H) 4.82 (m, 1 H) 6.95 (q, ^=8.20 Hz, 1 H) 7.01 (d,J=9.04Hz, 2H) 7.47 (m, 2H) 7.57 (m, 2H) 7.96 (m, 1 H) 8.16(m, 1 H) 8.96 (s, 1H) 9.07 (s, 1 H) 9.81 (s, 1 H). MS (ESI+) for C22H24N2O4S m/z 413.4 (M+H)+. HPLC 97%, £f=2.713 min (System Al, 10-97% MeCN over 3 min). EXAMPLE 37 5-fluoro-2-mef&yI-N-{4-0piperidiii-4-yloxy)-l-DaplitbyIIbenzenesuIfoDamide hydrochloride (General method F) The compound was prepared from intermediate 10 (0,24 g, 0.47 mmol). Yield: 0.21 g (9 9 %) of the title compound as an off-white solid. HPLC 100 %, R-r=1.823 min (System Al, 10-97 % MeCN over 3 mm). 'H NMR (400 MHz, O^C-H-d*) 5 ppm 2.13(m,4H)2.42(s,3H)3.18(m,2H)3.37(m,2H)4.83(m,lH)6.81(d,^8.53Hz, 1 H) 6.97 (d, >8.03 Hz, 1 H) 7.10 (m, 1H) 7.24 (m,J"=8.53,5.52 Hz, 1 H) 7.35 (m, 3 H) 7.83 (m, 1H). MS (ESI+) for C22H23FN2O3S m/z 415.2 (M+H)+. HPLC 96 %, R^l .628 min (System Bl, 10-90% MeCN over3mra). EXAMPLE 38 5-ChIor^N-H-(piperi hydrochloride (General method F) The compound was prepared from tert-butyl 4-[(4-{[(5-fluoro-2 methylphenyl)- sulfonyl]araino}-l-naphthyl)oxy]piperidine-l-carboxylate (0.24 g, 0.46 mmol). Yield: 0.16 g (76 %) of the title compound as a white solid. *H NMR (400 MHz, DMSO-de) 5 ppm 1.96-2.03 (m, 2 H) 2.16-2.22 (m, 2 H) 3.09-3.14 (m, 2 H) 3.25-3.31 (m, 2 H) 4.86-4.89 (m, 1 H) 7.04-7.11 (m, 2 H) 7.16 (d, .£=4.02 Hz, 1 H) 7.26 (d, >4.02Hz, 1H) 7.48-7.53 (m, 2 H) 7.92-7.94 (m, 1 H) 8.19-8.21 (m, 1 H) 9.06 (br s, 1 H) 10.36 (br s, 1 H). MS (ESI+) for C,9H,9C1N20JS2 m/z 423.0 (M+H)+. HPLC 99 %, Rr=1.861 min (System Al, 10-97 % MeCN over 3 min). EXAMPLE 39 4-Chloro-N-{4-[(3S>pyrrolidin-3-yloxy]-l-naphthyl}benzenesulfoHaiiiide hydrochloride (General methodF) The compound was prepared from tert-butyl (3S)-3-[(4-{[(4-cUorophenylJsulfonylJaminoJ-l-naphlhyi^xyJpyiroiidine-l-carboxylate (0.22 g, 0.44 mmol). Yield: 0.15 g (78 %) of the title compound as a yellow solid. *H NMR (400 MHz, CHjOH-cU) 8 ppm 2.37-2.49 (m, 2 H) 3.52-3.56 (m, 2 H) 3.61-3.71 (m, 2 H) 5.37 (br s, 1 H) 6.87 (d, >8.03 Hz, 1 H) 7.14 (d, ^8.03 Hz, 1 H) 7.38-7.47 (m, 4 H) 7.61 (d, J=%.5Z Hz, 2 H) 7.83 (d,J"=8.03 Hz, 1 H) 8.22 (d, /=8.03 Hz, 1H). MS (ESI+) for CsoHigClNaOjS mk 403.2 (M+H)+. HPLC 10Q %, RT=1 .826 min (System Al, 10-97 % MeCN over 3 min). EXAMPLE 40 4-Chloro-N-{4-[(3R>-pyrrolidin-3-yloxy]-I-aaphthyI}ben2enesiiIftinamide hydrochloride (General method F) The compound was prepared from tert-butyl (3R)-3-[(4-{[(4-cMorophenyl)sulfonyl]amino}-l-naphmyl)oxy]pyrK)lidine-l-carboxylate (0.37 g, 0.74 mmol). Yield: 0.27 g (82 %) of the title compound as a off-white solid. ]H NMR (400 MHz, CH3OH-G4) 8ppm2.37-2.49 (m, 2H) 3.52-3.56 (m, 2H) 3.61-3.71 (m, 2H) 5.37 (br s, 1 H) 6.88 (d, J=8.53 Hz, 1H) 7.15 (d, J=8.03 Hz, 1H) 7.39-7.47 (m, 4H)7.60-7.62 (m, 2 H) 7.83 (d, J=7.53 Hz, 1 H) 8.22 (d, J=8.03 Hz, 1 H). MS (ESI+) for CzoHisCD^OsS ra/z 403.2 (M+H)*. HPLC 100 %, RT=1.815 min (System Al, 10-97 % MeCN over 3 min). Table 4 WE CLAIM: 1. A compound of the formula (I): or a pharmaceutical ly acceptable salt thereof, wherein: eachWis-(CH)-,or-Cs P is any one of formula (a), (b) or (c) and P and R can be attached to any carbon atom that allows the substitution in one of either the A- or B-ring; the dashed bonds denote that P and R, respectively, may be attached to either the A or B ring; but each P or R may not be simultaneously bound to both rings A and B; R'is (a) C1.6 alkyl, (b) C].5 alkoxyalkyl, (c) straight-chained or branched C1.g hydroxyalkyl, (d) straight-chained or branched Cj.g alkylhalides, (e) aryl carbonylmethyl, (0 C3.7 cycloalkyl, which is optionally partially unsaturated, (g) C3.7 cycloalkyl-C] alkyl, wherein the cyclic ring is optionally partially unsaturated, or (h) a group Ar; wherein Ar is (a) phenyl, (b) 1-naphthyl, (c) 2-naphthyl, (d) aryl-C1 alkyi, (e) cinnamyl, (f) a 5 to 7-membered, optionally aromatic, partially saturated or completely saturated, mono- or bi-cyclic heterocyclic ring, each containing 1 to 4 heteroatoms, selected from oxygen, sulfur, and nitrogen, (g) a bicyclic ring system comprising at least one heterocyclic ring according to (f) and a group Ar, wherein the group Ar is substituted in one or more positions with (a) H, X or Y, or (b) a 5 to 7-membered, optionally aromatic, partially saturated or completely saturated, heterocyclic ring each containing 1 to 4 heteroatoms selected from oxygen, nitrogen or sulfur; Ris (a)H, (b)C1.6 alkyl, (c) C2-6 alkoxyalkyl, (d) straight or branched C1-6 hydroxyalkyl, or (e) straight or branched C1.6 alkylhalides; (f) a group Ar, X and Y are independently (a)H, (b) halogen, (c)C|-6alkyl, (d) CF3, (e) hydroxy, (0 C1-6 aJkoxy, (g) C2-6 alkenyl, (h) phenyl, (i) phenoxy, (j) benryloxy, (k) benzoyl, (I) -OCF3, (m) -CN, (n) straight or branched C| hydroxyalkyl, (0) straight or branched C1-6 alkylhalides, (P)-NH2, (q)-NHR(r) -NR-'R (s) -NO,, (t) -CONR'R (u) -NHSO2R', (v) -NR'COR', (x) -S02NR'R (z)-C(=0)R (k) -C02R or (l) -S(0)nR wherein n is 0, 1, 2 or 3, (ac)-S-(C,.6)alkyl,or (ad) -SCF3; and R* and R are independently (a)H, Cb)C1-6alkyl, (c) C3.7 cycloalkyl, or (d) Ar, as defined above for R' ; alternatively, R"* and R are linked to form a group -CH2OCH2-, -CH2CH2OCH2CH2- or (CH2)3.5; wherein R is optionally substituted on each carbon atom that allows the substitution with Rq groups, wherein Rq is independently H, or (C|) alkyl, and wherein two Rq groups can be present on the same carbon atom simultaneously, wherein q=l,2, 3,4, 5or6, m = 1 or 2, and n = 0, 1 or 2; R* is independently (a)H, (b) linear or branched C1.6 alkyi, (c) benzyl, (d) -CH2-CH2-OH, or (e)-CH2-CH2-0-CMalk:'' P and R can be attached to the same ring or to different rings of rings A and B; when R' = Ar is partially saturated bi-cyclic heterocyciic ring containing a N atom, the N atom in Ar cannot be attached to the S atom in P; and with the proviso that: when P is of formula (a) substituted in position 7 on the naphthalene ring, then R is not substituted in position 1 on the naphthalene ring. 2. The compound according to claim 1, wherein R'is (a)C1.6alkyl, or (e) a group Ar; Ar is (a) phenyl, (b) 1-naphthyl, (c) 2-naphthyl, or (f) a 5 to 7-membered, optionally aromatic, partially saturated or completely saturated, heterocyclic ring containing 1 to 4 heteroatoms, selected from oxygen, nitrogen and sulfur, wherein the group Ar is substituted in one or more positions with (a)H, (b) halogen, (c) C, alkyl, {d)-CF,, (f)C,_6alkoxy, (g) C2.6 alkenyl, (1) -0CF3, (m) straight or branched C|.6 hydroxyaikyl, (n) phenyloxy, (o) benzyloxy, (v) -NR'COR (x) -SOjNRR (z)-C(-0)R (ab) -S(0)nR', wherein n is 0, 1, 2 or 3; (ac)-S-(C].6)alkyl, or (ad)-SCF3; RMS (a) H, or (b)C,.6alkyi; or R' and R are linked to form a group -CH2CH2OCH2CH2-; X and Y are H; R and R are each independently H or C1-3 alkyl; and wherein R can be substituted on each carbon atom that allows the substitution with Rq groups, wherein Rq is independently H, or C 1.6 alkyl, and wherein two Rq groups can be present on the same carbon atom simultaneously, wherein q = 1 or 2, m = 1 or 2, n 0, and R* is independently (a)H, (b) C1-6 alkyl, in particular methyl, (d) -CH2-CH2-OH, or (e)-CH2-CH2-OCH3. 3. A compound according to any one of claims 1 to 2 wherein R is H or methyl. 4. The compound according to any one of claims 1 to 3 wherein the groups Y and X are attached to any unsubstituted carbon atom. 5. The compound according to any one of claims 1 to 4, wherein R is H. wherein P, R X and Y are as defined in claim I. 7. A compound according to claim 6, which is the compound 4-Chloro-N-[4-{pyiToiidin-3-yioxy)-l-naphthyl]ben2enesulfonamide hydrochloride; 4-Methoxy-N-[4-{pyrrolidin-3-yloxy)-l-naphthyl]benzenesulfonamide hydrochloride; 5-Chloro-N-[4-(pyrrolidin-3-yloxy)-l-naphthyl]thiophene-2-sulfonamide hydrochloride; 4-Chloro-N-[4-(piperidin-3-y!oxy)-l-naphthyl]benzenesulfonamide hydrochloride; 4-Methoxy-N-[4-(piperidin-3-y!oxy)-l-naphthyl]benzenesuifonamide hydrochloride; 5-Fiuoro-2-methyl-N-[4-(piperidin-4-yloxy)-l-naphthyl]benzenesulfonamide hydrochloride; 5-Chloro-N-[4-(piperidin-4-yloxy)-I-naphthyl]thiophene-2-sulfonamide hydrochloride; 4-Chloro-N-{4-[(3S)-pyrrolidin-3-yloxy]-l-naphthyl}benzenesulfonamide hydrochloride; or 4-Chloro-N-{4-[(3R)-pyrrolidin-3-yloxy]-l-naphthyl}benzenesuSfonam\de hydrochloride. 8. A pharmaceutical formulation comprising a compound according to any one of claims 1 to 7 as an active ingredient, in combination with a phamiaceutically acceptable diluent or carrier.

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