Title of Invention	A PROCESS FOR THE PREPARATION OF NOVEL 1-[(4-DIPHENYLMETYL)-PIPERAZIN-1-YL]-3-ARYLOXYPROPAN-2-OL
Abstract	The present invention provides a novel compound l-[(4-Diphenylmetyl)-piperazin-l-yl]-3-aryloxypropan-2-ol and their pharmaceutically acceptable hydrochloride salts useful as antihistaminic agent. The present invention further provides a process for the preparation of novel l-[(4-diphenylmetyl)-piperazin-l-yl]-3-aryloxypropan-2-ols and their use in combating the symptoms of histaminic disorders.

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The present invention relates to a process for the preparation of novel compound 1-[(4-Diphenylmetyl)-piperazin-l-yl]-3-aryloxypropan-2-ol and their pharmaceutically acceptable hydrochloride salts useful as antihistaminic agent. The present invention particularly relates to the synthesis of novel l-[(4-diphenylmetyl)-piperazin-l-yl]-3-aryloxypropan-2-ols of general formula 3 and their use in combating the symptoms of histaminic disorders. Antihistamines became widely used in the mid to late 1940. They are used in the treatment of various allergic disorders, particularly rhinitis, conjunctivitis and urticaria. These antihistaminics do have some serious side effects, the most notable being their central nervous system depressant activity in the therapeutic doses. The problem of sedation limited the use of chemical antihistamines, and the search of Hi-antagonists without sedative potential has been a key goal within the pharmaceutical industry. Several non sedating Hr antihistamines have been introduced in the clinic and others are under investigation and continuously emerging from the patent literature. The highest incidence of side effect is sedation with the first generation H1 antagonists, which is not a feature of the second-generation agents. The most frequent side effect involves the digestive tract and include loss of appetite, nausea, dryness of mouth etc, these effects are not observed with the second generation H1 antagonists Cetirizine is the 2nd generation Ht antagonist, has negligible penetration into the brain but is associated with some what higher incidence of drowsiness than the other 2nd generation H1 antagonists. Therefore research is being continued for the newer antihistaminics with fewer side effects. Novel compound l-[(4-Diphenylmetyl)-piperazin-l-yl]-3-aryloxypropan-2-ol is disclosed and claimed in our co-pending patent application no. 497Nf2004. The main objective of present invention is to provide novel and potent antihistaminic agents. Another objective of the present invention is to provide a novel l-[(4-Diphenylmetyl) -piperazin-l-yl]-3-aryloxypropan-2-ols of the formula 3. Yet another object is to provide a process for the preparation of novel l-[(4-Diphenyl metyl)-piperazin-l-yI]-3-aryloxypropan-2-ols of general formula 3. Accordingly the present invention provides novel l-(4-benzhydryl piperzin-l-yl)-3- aryloxypropan-2-ol of general formula 3 (Formula Removed) wherein R and Rl are H or CI and R2 is selected from the group consisting of 2, 3, or 4 trifluoromethyl, 2,3,or 4 chloro, 2,3 or 4 bromo, 4-acetyl, 4-propionyl, 4-acetamido, 2,3,or 4-methoxy, 4-nitrile, 2 or 4-methyl, 4-bromo and 2,3, or 4-methoxyl, useful as an antihistaminic agent. In another embodiment the present invention the novel l-(4-benzhydryl piperzin-1-yl)-3-aryloxypropan-2-ol of general formula 3 obtained is selected from the group consisting of 3a: 1 -[(4-Diphenylmetyl)-piperazin-1 -yl]-3-phenoxy-propan-2-ol 3b: l-[(4-Diphenylmetyl)-piperazin-l-yl]-3-(4-chloro-phenoxy)-propan-2-ol 3c: 1 -[(4-Diphenylmetyl)-piperazin-1 -yl]-3-(4-acetamido-phenoxy)-propan-2-ol 3d: 1 -[(4-Diphenylmetyl)-piperazin-1 -yl]-3-(4-cyano-phenoxy)-propan-2-ol 3e: l-[(4-Diphenylmetyl)-piperazin-l-yl]-3-(4-bromo-phenoxy)-propan-2-ol 3f: l-[(4-Diphenylmetyl)-piperazin-l-yl]-3-(2-methyl-phenoxy )-propan-2-ol 3g: 1 - { 4-[(4-chlorophenyl)-phenyl-mehtyl]-piperazin-1 -yl-3-phenoxy-propan-2-ol 3h: 1 - {4-[(4-chlorophenyl)-phenyl-mehtyl]-piperazin-l -yl} -3-(3-a,a,a-trifluoromethyl-phenoxy)-propan-2-ol 3i: 1 - {4-[(4-chlorophenyl)-phenyl-methyl]-piperazin-1 -yl} -3-(4-acetamido-phenoxy)- propan-2-ol 3j: 1- {4-[(4-chlorophenyl)-phenyl-methyl]-piperazin-1 -yl} -3-(4-acetyl-phenoxy)- propan-2-ol 3k: 1 - {4-[(4-chlorophenyl)-phenyl-methyl]-piperazin-l -yl} -3-(2-metoxy-phenoxy)- propan-2-ol 31:1- {4-[(4-chlorophenyl)-phenyl-methyl] -piperazin-1 -yl} -3-(2-methyl-phenoxy)- propan-2-ol 3 m: 1 - {4-[(4-chlorophenyl)-phenyl-methyl]-piperazin-1-yl}-3-(3-methoxy-phenoxy)- propan-2-ol 3n: l-{4-[(4-chlorophenyl)-phenyl-methyl]-piperazin-l-yl}-3-(4-propionyl-phenoxy)- propan-2-ol 3o: 1 - {4-[(4-chlorophenyl)-phenyl-methyl]-piperazin-l -yl} -3-(4-cyano-phenoxy)- propan-2-ol 3p:l-{4-[(4-chlorophenyl)-phenyl-methyl]-piperazin-l-yl}-3-(4-bromo-phenoxy)- propan-2-ol 3q: 1 - {4-[(4-chlorophenyl)-phenyl-methyl]-piperazin-1 -yl} -3-(2-naphthyloxy)- propan-2-ol 3r: 1 - {4-Bis-[(4-chlorophenyl)-methyl]-piperazin-1 -yl} -3-(4-bromo-phenoxy)- propan-2-ol 3s: 1 - {4-Bis-[(4-chlorophenyl)-methyl]-piperazin-1 -yl} -3-(3-metoxy-phenoxy)- propan-2-ol 3t: 1 -{4-Bis-[(4-chlorophenyl)-methyl]-piperazin-l-yl}-3-(3-a,a,a-trifluromethyl - phenoxy)-propan-2-ol 3u:l-{4-Bis-[(4-chlorophenyl)-methyl]-piperazin-l-yl}-3-(4-acetyl-phenoxy)-propan- 2-ol 3v: 1 - {4-Bis-[(4-chlorophenyl)-methyl]-piperazin-l -yl} -3-(3-methyl-phenoxy)- propan-2-ol 3w: l-{4-Bis-[(4-chlorophenyl)-methyl]-piperazin-l-yl}-3-phenoxy)-propan-2-ol 3x:: 1 - {4-Bis-[(4-chlorophenyl)-methyl]-piperazin-l -yl} -3-(4-cyanophenoxy)-propan- 2-ol 3y: 1 - {4-Bis-[(4-chlorophenyl)-methyl]-piperazin-1 -yl} -3-(4-propionylphenoxy)- propan-2-ol 3z: l-{4-Bis-[(4-chlorophenyl)-methyl]-piperazin-l-yl}-3-(2-methoxy-phenoxy)- propan-2-ol. The present invention further provides a process for the preparation of novel l-(4-benzhydryl piperzin-l-yl)-3-aryloxypropan-2-ols of general formula 3, (Formula Removed) wherein R and Rl are H or CI and R2 is selected from the group consisting of 2, 3, or 4 trifluoromethyl, 2,3,or 4 chloro, 2,3 or 4 bromo, 4-acetyl, 4-propionyl, 4-acetamido, 2,3,or 4-methoxy, 4-nitrile, 2 or 4-methyl, 4-bromo and 2,3, or 4-methoxyl, which comprise reacting diphenyl methyl piperazine of formula 1, wherein R and Rl are H or CI, with an aryloxy epoxy propane of formula 2, wherein R2 is selected from the group consisting of 2, 3, or 4 trifluoromethyl, 2,3,or 4 chloro, 2,3 or 4 bromo, 4-acetyl, 4-.propionyl, 4-acetamido, 2,3,or 4-methoxy, 4-nitrile, 2 or 4-methyl, 4-bromo and 2,3, or 4-methoxyl, at a temperature in the range of 90-100°C in an inert organic solvent, distilling off the solvent from the above said reaction mixture and purification of the resultant product by known method to obtained the desired product of general formula 3, or its pharmaceutically accepted hydrochloride salt by adding hydrochloric acid to the compound of general formula 3. In yet another embodiment the inert organic solvent used is an aliphatic alcohol and or an aprotic solvent selected from the group consisting of ethanol, methanol, propanol, isopropanol and acetonitrile. In yet another embodiment the novel l-(4-benzhydryl piperzin-l-yl)-3-aryloxypropan 2ols of general formula 3 obtained is selected from the group consisting of 3a: 1 -[(4-Diphenylmetyl)-piperazin-1 -yl]-3-phenoxy-propan-2-ol 3b: l-[(4-Diphenylmetyl)-piperazin-l-yl]-3-(4-chloro-phenoxy)-propan-2-ol 3c: 1 -[(4-Diphenylmetyl)-piperazin-1 -yl]-3-(4-acetamido-phenoxy)-propan-2-ol 3d: l-[(4-Diphenylmetyl)-piperazin-l-yl]-3-(4-cyano-phenoxy)-propan-2-ol 3e: l-[(4-Diphenylmetyl)-piperazin-l-yl]-3-(4-bromo-phenoxy)-propan-2-ol 3f: 1 -[(4-Diphenylmetyl)-piperazin-l -yl]-3-(2-methyl-phenoxy )-propan-2-ol 3g: 1 - {4-[(4-chlorophenyl)-phenyl-methyl]-piperazin-1 -yl-3-phenoxy-propan-2-ol 3h:l-{4-[(4-chlorophenyl)-phenyl-methyl]-piperazin-l-yl}-3-(3-a,a,a- trifluoromethyl-phenoxy)-propan-2-ol 3i: 1 - {4-[(4-chlorophenyl)-phenyl-methyl]-piperazin-1 -yl} -3-(4-acetamido-phenoxy)- propan-2-ol 3j: 1 - {4-[(4-chlorophenyl)-phenyl-methyl]-piperazin-1 -yl} -3-(4-acetyl-phenoxy)- propan-2-ol 3k: 1 - {4-[(4-chlorophenyl)-phenyl-methyl]-piperazin-l -yl} -3-(2-metoxy-phenoxy)-. propan-2-ol 31:1- {4-[(4-chlorophenyl)-phenyl-methyl]-piperazin-1 -yl} -3-(2-methyl-phenoxy)- propan-2-ol 3m:l-{4-[(4-chlorophenyl)-phenyl-methyl]-piperazin-l-yl}-3-(3-methoxy-phenoxy)- propan-2-ol 3n:l-{4-[(4-chlorophenyl)-phenyl-methyl]-piperazin-l-yl}-3-(4-propionyl-phenoxy)- propan-2-ol 3 o: 1 - {4- [(4-chlorophenyl)-phenyl-methyl] -piperazin-1 -yl} -3 -(4-cyano-phenoxy)- propan-2-ol 3p: 1 - {4-[(4-chlorophenyl)-phenyl-methyl]-piperazin-1 -yl} -3-(4-bromo-phenoxy)- propan-2-ol 3q: 1 - {4-[(4-chlorophenyl)-phenyl-methyl]-piperazin-1 -yl} -3-(2-naphthyloxy)- propan-2-ol 3r: 1 - {4-Bis-[(4-chlorophenyl)-methyl]-piperazin-1 -yl} -3-(4-bromo-phenoxy)- propan-2-ol 3s: 1 - {4-Bis-[(4-chlorophenyl)-methyl]-piperazin-1 -yl} -3-(3-metoxy-phenoxy)- propan-2-ol 3t: l-{4-Bis-[(4-chlorophenyl)-methyl]-piperazin-l-yl}-3-(3-a,a,a-trifluromethyl - phenoxy)-propan-2-ol 3u: 1 - {4-Bis-[(4-chlorophenyl)-methyl]-piperazin-1 -yl} -3-(4-acetyl-phenoxy)-propan- 2-ol 3v:l-{4-Bis-[(4-chlorophenyl)-methyl]-piperazin-l-yl}-3-(3-methyl-phenoxy)- propan-2-ol 3w: 1 - {4-Bis-[(4-chlorophenyl)-methyl]-piperazin-1 -yl} -3-phenoxy)-propan-2-ol 3x:: 1 - {4-Bis-[(4-chlorophenyl)-methyl]-piperazin-1 -yl} -3-(4-cyanophenoxy)-propan- 2-ol 3y: 1 - {4-Bis-[(4-chlorophenyl)-methyl]-piperazin-1 -yl} -3-(4-propionylphenoxy)- propan-2-ol 3z: l-{4-Bis-[(4-chlorophenyl)-methyl]-piperazin-l-yl}-3-(2-methoxy-phenoxy)- propan-2-ol. In yet another embodiment the compounds l-(4-benzhydryl piperzin-l-yl)-3-aryloxypropan-2-ols of general formula 3 shows significant antihistaminic activity. In yet another embodiment the compounds 3 a to 3j obtained shows significant in vivo antihistaminic activity when administered individually or in combination thereof in a dose ranging from 2-13 mg/Kg. In yet another embodiment the compound 3d exhibits in vitro antihistaminic activity of a maximum of 56% and 90% response with the doses of O.lug/mL and 1.0µg dose/mL. respectively, in an organ bath containing tyrode solution through guinea pig ileum (GPI) ' assay. The following examples are given by the way of illustration and should not be construed to limit the scope of present invention. Example 1 l-(4-trifluoromethylphenoxy)-2,3-epoxypropane: A mixture of 4-trifluoromethyl phenol (2g, 12mmol.), K2CO3 (2.04g, 14.4mmol.) and epichlorohydrin (lOmL) was stirred at 120°C for 4 hrs. After completion of reaction, the solid was filtered; filtrate was diluted with water (50mL) and extracted with ethylacetate (3x25mL). Organic layer was washed with distilled water (3xl00mL) and concentrated to oil, which was purified on silica gel column using hexane: ethyl acetate (9:1) as eluant, to give the required compound 2.42g (90%) yield. 1H NMR(200MHz,CDCI3): δ 2.75-2.79(m,lH,C-3H), 2.90-2.95(m,lH,C-3H), 3.34- 3.38(m,lH,C-2H), 3.93-4.01(dd,lH,J=11.0Hz,J=5.8Hz,C-lH), 4.26-4.33 (dd, 1H,J=11.1HZ,J=2.9HZ,C-1H), 6.96-7.00(d,2H,J=8.5Hz,2 & 6-ArH), 7.52-7.57 (d,2H,J=8.6 Hz,3&5ArH). MS(m/z): 218 (Ivf, 100%), 199,188. Similarly other substituted aryloxy epoxypropanes were prepared by substituting the 4- trifluoromethyl phenol by an equivalent amount of substituted phenol (/. Med .Chem. 1972,15 ,No.3,286-291.) Example 2 4-(4-benzhydrylpiperazin-l-yl)-3-(4-cyano-phenoxy)-propan-2-ol(3d): A mixture of 504mg (2mmol) of l-(diphenylmethyl)piperazine and and 4-.acetamidophenoxyepoxypropane 455mg (2.2mmol) in 15 mL absolute alcohol was refluxed for 8 hrs at 90°C. Reaction was monitored by tic There after solvent was distilled off and r residual oily mass was purified on silica gel column using CH3OH : CHCI3 (1:99) mixture as an.eluent. The pure compound 3d was obtained as off white solid, 846mg (91% yield), m.p. 136-138°C, converted to hydrochloride salt (m.p. 290°C). IR(Neat):3429, 3020, 2943, 2818, 2227,1804,1606,1508,1217. MS (FAB) m/z: 460 (M++l, 50%), 441 (M+-18), 325 (M+-134). 1H NMR (200 MHz, CDCI3,δ): 2.06 (s, 3H, COCH3), 2.37-2.49 (m, 8H, piperazinyl), 2.55-2.63 (m, 2H, NCH2), 3.85-3.87 (d, 2H, J = 4.6Hz, OCH2), 3.91-4.00 (m, 1H, CHOH), 4.5 (s, 1H, CH (Φ)2), 6.76-6.80 (d, 2H, J = 8.74 Hz, ArH ortho to O), 7.06-7.36 (m, 12H, ArH). Similarly 3a, 3b, 3c, 3e, & 3f were prepared using appropriately substituted phenoxy epoxypropanes. Example 3 l-{4-[(4-chlorophenyl)-phenyl-mehtyl]-piperazin-l-yl}-3-(4-acetamido-phenoxy)-propan-2-ol(3i): A mixture of l-[(4-chlorophenyl) phenyl methyl piperazine 574mg (2 mmol) & 4-acetamido phenoxy epoxypropane 460mg (2.22mmol) in absolute ethanol was refluxed under stirring at 90°C for 8 hrs. Reaction was monitored by tic. There after the reaction mixture was concentrated to give an oily mass, which was purified on silica gel chromatographic column. 875mg (85%yield) of l-{4-[(4-chlorophenyl)-phenyl-methyl]-piperazin-l-yl}-3-(4-acetamido-phenoxy)-propan-2-ol (3i) was obtained as white solid m.p. 83°C. Hydrochloride salt was prepared. IR(KBr): 3297, 2958, 2816,2368, 1629, 1511, 1408, 1242,1093. MS (FAB) m/z: 494(M+1), 460(M+-34), 307, 201. 1H NMR (200MHz,CDCl3,δ): 2.14 (s, 3H, CH3), 2.43-2.61 (m, 8H, piperazinyl), 2.66-2.69 (d, 2H, NCH2, J=6.2Hz), 3.92-3.94 (d, 2H, 0-CH2, J=8.5Hz), 4.03-4.05 (m, 1H, CHOH), 4.211 (s, 1H, CH(C6H5)2, 6.84-6.88 (d, 2H, ArH, J=8.8Hz), 7.18-7.38 (m, 1H, ArH). Similarly 3g, 3h, 3k-3q were prepared from l-[(4-chlorophenyl) phenyl methyl piperazine. and appropriately substituted phenoxyepoxy propanes. Example 4:- {4-Bis-[(4-chlorophenyl)-mehtyl]-piperazine-l-yl}-3-(4-acetyl-phenoxy)-propan-2- ol(3u):- ' A mixture of 4, 4'-dichlorobenzhydryl piperazine 642mg (2mmol )and 4-acetyl phenoxy epoxypropane 422mg (2.2mmol)in absolute ethanol was refluxed under stirring at 100°C for 8hrs till the reaction was complete. Reaction was monitored by tic. There after the reaction mixture was concentrated to give an oily mass, which was purified on silica gel column. The pure compound was obtained using CH3OH: CHCl3(l:99)mixture as eluant in 76% yield, 784 mg as colourless oil was converted to HC1 salt. IR(Neat): 3431, 2941, 2818, 1670, 1599, 1418, 1257, 1172. MS (FAB) m/z: 514(M+1), 513(M*), 401,333. 1H NMR (200MHz, CDC13,δ): 2.43-2.54 (m,8H, piperazinyl), 2.64 (s, 3H, COCH3), 2.67-2.70 (m, 2H, NCH2), 3.76-3.77 (m, 2H, OCU2), 4.03-4.17 (m, 1H, CHOH), 4.25 (s, 1H, CH( 6.92-6.99 (m, 2H, ArH), 7.22-7.36 (m, 8H, ArH), 7.89-7.96 (m, 2H, ArH). Similarly compounds 3r-3z were prepared using appropriate substituted phenoxy epoxypropanes. The pharmacological evaluation of the test compounds of general formula 3 was carried out by the following protocol. A- In vitro antihistaminic activity evaluation: The antihistaminic activity of the series of novel l-[(4-Diphenylmetyl)-piperazin-l-yl]-3-aryloxypropan-2-ols 3a-3z have been evaluated using guinea pig ileum (GPI) assay. A small piece of 2-3cm of the terminal part of the G. Pig ileum was mounted in an organ bath (10ml) containing tyrode solution (sodium chloride 8.0g, potassium chloride 0.2g, magnesium sulphate 0.2g and glucose 1.0g / per liter of distilled water) maintained at a temperature of 36+1 °C and saturated with oxygen. The GPI contractions were recorded via a gross force transducer on one of the channel of polygraph. GPI contractions were induced by the sub maximal concentration of histamine. The histamine was allowed to act 30 sec prior to wash. The histamine basal response was obtained prior to assessing histamine blocking activity of test compounds then graded concentrations (0.05-5|^g/ml) of the test compound were added one minute prior to addition of the histamine in the bath and percent inhibition of histamine induced contraction of GPI for each dose was calculated. The compounds showing significant antihistaminic response were tested with doses ranging from 0.05-5|j.g/ml at least in 3-4 preparations. The percent antihistaminic response was calculated by averaging the response pattern at each dose level, and has been summarized in Table-1. Table 1: Percent Antihistaminic activity in GPI Assay:- (Table Removed) Histamine dose: l 0µg/ml and each value in the table is mean value of 4-5 responses Compound 3c at various doses was slightly less active as compared to 3d. Compound 3d produced dose dependent antihistaminic activity and the lowest dose 0.01µg/mL produced 40% antihistaminic activity. A dose of 0.lµg/ml produced 56% response, which was increased in a dose dependent manner with maximal antihistaminic effect 90% with 1.0µg dose. Further increasing doses did not significantly affect histamine induced GPI contractile response may be due to saturation of histamine receptors. Other compounds 3c, 3f, 3i, 3j and 3a had marked antihistaminic activity and it was better or comparable to reference drug cetirizine at the various doses ranging from 0.05 to 2 µg/ml (Table-1). Thus it appears that all the six compounds are potent antihistaminics representing chemical novelty. B- In vivo antihistaminic activity evaluation:- PCA ( Passive cutaneous anaphylaxis) in rats was carried out according to following protocol (Ind.J.Exp.Biolog.39. 2001,871-877):- The egg albumin (EA) was used as antigen. Rat antiserum was prepared by sensitizing them on 1st, 3rd and 5th day. On 10th day of sensitization, serum was separated from the blood taken from the orbital plexus of rats and 1:10 dilution of serum containing IgE type of antibodies was used for sensitization. Male SD rats were sensitized intradermally on their shaved backs with 0.1 ml of antiserum containing IgE. After 48 hours of sensitization, test compounds (0.5 to 7.5 mg/kg) and standard drug (50 mg/kg) were given orally and by intraperitoneal routes respectively .One hour later 1% egg albumin along with 0.5% Evan's blue (0.25 ml each) were administered intravenously. After half to one hour, the inhibitory effects of test compounds were measured as the percent reduction in dye leakage area and compared with that of vehicle treated animals. The anti PCA activity of active compounds viz, 3a, 3c, 3d, 3f, 3i and 3j was evaluated to claim a broad based antihistaminic profile. The results indicate that these compounds show significant antiallergic activity (TabIe-2). The combined effect of two active compounds at lower doses was also studied. Compound 3d at lower doses 2.5 and 5mg /Kg was coadministered with 10 and 5mg/Kg of 3i. Both together seem to produce synergistic antihistaminic effect as determined by anti PCA test (Table-3). Table 2: The anti PCA activity in rats using rat homologous antiserum (Table Removed) Table 3: Bioevaluation of Synergistic activity of antiWstarninic compounds by Anti PCA test:- (Table Removed) The advantages of the present invention are: 1. It provides novel compounds, which are useful as antihistaminic agents. 2. The compounds prepared are simple than the existing drug cetirizine. 3. The starting materials used for the preparation of novel compounds are cheap and are easily available. 4. The process described herein for the preparation of novel compounds is simple, economically feasible and ecofriendly. We claim 1. A process for the preparation of novel 1 -(4-benzhydryl piperzin-l-yl)-3- aryloxypropan-2-ols of general formula 3, (Formula Removed) wherein R and Rl are H or C1 and R2 is selected from the group consisting of 2, 3, or 4 trifluoromethyl, 2,3,or 4 chloro, 2,3 or 4 bromo, 4-acetyl, 4-propionyl, 4-acetamido, 2,3,or 4-methoxy, 4-nitrile, 2 or 4-methyl, 4-bromo and 2,3, or 4-methoxyl, which comprise reacting diphenyl methyl piperazine of formula 1, wherein R and Rl are H or C1, with an aryloxy epoxy propane of formula 2, wherein R2 is selected from the group consisting of 2, 3, or 4 trifluoromethyl, 2,3,or 4 chloro, 2,3 or 4 bromo, 4-acetyl, 4-propionyl, 4-acetamido, 2,3,or 4-methoxy, 4-nitrile, 2 or 4-methyl, 4-bromo and 2,3, or 4-methoxyl, at a temperature in the range of 90-100°C in an inert organic solvent, distilling off the solvent from the above said reaction mixture and purification of the resultant product by known method to obtained the desired product of general formula 3, or its pharmaceutically accepted hydrochloride salt by adding hydrochloric acid to the compound of general formula 3. 2. A process as claimed in claim 1, wherein the inert organic solvent used is an aliphatic alcohol and or an aprotic solvent selected from the group consisting of ethanol, methanol, propanol, isopropanol and acetonitrile. 3. A process as claimed in claims 1&2, wherein the compound l-(4-benzhydryl piperzin-l-yl)-3-aryloxypropan-2-ol obtained is a derivative, analogue or in salt forms. 4. A process as claimed in claims 1-3, wherein the novel l-(4-benzhydryl piperzin-l-yl)-3-aryloxypropan-2-ols of general formula 3 obtained is selected from the group consisting of 3a: l-[(4-Diphenylmetyl)-piperazin-l -yl]-3-phenoxy-propan-2-ol 3b: 1 -[(4-Diphenylmetyl)-piperazin-1 -yl]-3-(4-chloro-phenoxy)-propan-2-ol 3c: 1 -[(4-Diphenylmetyl)-piperazin-1 -yl]-3-(4-acetamido-phenoxy)-propan-2-ol 3d: l-[(4-Diphenylmetyl)-piperazin-l-yl]-3-(4-cyano-phenoxy)-propan-2-ol 3e: l-[(4-Diphenylmetyl)-piperazin-l-yl]-3-(4-bromo-phenoxy)-propan-2-ol 3f: l-[(4-Diphenylmetyl)-piperazin-l-yl]-3-(2-methyl-phenoxy)-propan-2-ol 3g: l-{4-[(4-chlorophenyl)-phenyl-methyl]-piperazin-l-yl-3-phenoxy-propan-2-ol 3h:l-{4-[(4-chlorophenyl)-phenyl-methyl]-piperazin-l-yl}-3-(3-α,α,α- trifluoromethyl-phenoxy)-propan-2-ol 3i:l-{4-[(4-chlorophenyl)-phenyI-methyl]-piperazin-l-yl}-3-(4-acetamido- phenoxy)-propan-2-ol 3j:l-{4-[(4-chlorophenyI)-phenyl-methyl]-piperazin-l-yl}-3-(4-acetyl-phenoxy)- propan-2-ol 3k: 1 -{4-.[(4-chlorophenyl)-phenyl-methyl]-piperazin-l -yl}-3-(2-metoxy- phenoxy)-propan-2-ol 31:1 - {4-[(4-chlorophenyl)-phenyl-methyl]-piperazin-1 -yl} -3-(2-methyl-phenoxy)- propan-2-ol 3m:l-{4-[(4-chlorophenyl)-phenyl-methyl]-piperazin-1-yl}-3-(3-methoxy- phenoxy)-propan-2-ol 3n:l-{4-[(4-chlorophenyl)-phenyl-methyl]-piperazin-l-yl}-3-(4-propionyl- phenoxy)-propan-2-ol 3o:l-{4-[(4-chlorophenyl)-phenyl-methyl]-piperazin-l-yl}-3-(4-cyano-phenoxy)- propan-2-ol 3p:l-{4-[(4-chlorophenyl)-phenyl-methyl]-piperazin-l-yI}-3-(4-bromo-phenoxy)- propan-2-ol 3q: 1 -{4-[(4-chlorophenyl)-phenyl-methyl]-piperazin-1 -yl }-3-(2-naphthyloxy)- propan-2-ol 3r:l-{4-Bis-[(4-chlorophenyl)-methyl]-piperazin-l-yl}-3-(4-bromo-phenoxy)- propan-2-ol 3s:l-{4-Bis-[(4-chlorophenyl)-methyl]-piperazin-l-yl}-3-(3-metoxy-phenoxy)- propan-2-ol 3t: 1 -{4-Bis-[(4-chlorophenyl)-methyl]-piperazin-1 -yl }-3-(3-α,α,α-trifluromethyl -phenoxy)-propan-2-ol 3u:l-{4-Bis-[(4-chlorophenyl)-methyl]-piperazin-l-yl}-3-(4-acetyl-phenoxy)- propan-2-ol 3v: 1 -{4-Bis-[(4-chlorophenyl)-methyl]-piperazin-1 -yl }-3-(3-methyl-phenoxy)- propan-2-ol 3w: l-{4-Bis-[(4-chlorophenyl)-methyl]-piperazin-l-yl}-3-phenoxy)-propan-2-ol 3x:: 1 -{4-Bis-[(4-chlorophenyl)-methyl]-piperazin-1 -yl} -3-(4-cyanophenoxy)- propan-2-ol 3y:l-{4-Bis-[(4-chlorophenyl)-methyl]-piperazin-l-yl}-3-(4-propionylphenoxy)- propan-2-ol 3z: 1 -{4-Bis-[(4-chlorophenyl)-methyl]-piperazin-1 -yl} -3-(2-methoxy-phenoxy)- propan-2-ol.

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2463-del-2005-abstract.pdf

2463-DEL-2005-Claims-(21-06-2012).pdf

2463-del-2005-claims.pdf

2463-DEL-2005-Correspondence Others-(21-06-2012).pdf

2463-del-2005-correspondence-others.pdf

2463-del-2005-description (complete).pdf

2463-del-2005-drawings.pdf

2463-del-2005-form-1.pdf

2463-del-2005-form-18.pdf

2463-del-2005-form-2.pdf

2463-del-2005-form-3.pdf

2463-del-2005-form-5.pdf