Patent EA-000722-B1 (EA)
Title: Use of pyrrolidine derivatives for treating alcoholism
Inventor: IMPERATO ASSUNTA
IPC: A61K31/425
Filed: 1996-05-29
Abstract: 1. Use of pirrolidine derivatives of formula (I)   wherein R represents either a methylene radical, SO or sulphur atom; R1 represents phenyl, which can be optionally substituted by one or a number of substituents selected from halogen atoms and hydroxyl radical; and R5 represents a hydrogen atom; R2 represents an alkoxycarbonyl; R3 represents phenylamino group phenyl core of which can be optionally substituted by one or a number of substituents selected from carboxyl, hydroxyiminoalkyl, hydroxyalkyl radicals, -alk-COOH-, -alk-SO3H as a salt, -S-alk-COOH; R4 represents a hydrogen atom; -alk represents alkylene radical wherein alkyl, alkylene and alkoxy radicals and the alkyl, alkylene and alkoxy portions contain 1 to 4 straight- or branched-chain carbon atoms, and salts thereof, or their racemates or enantiomers, if they contain at least one asymmetric center to obtain a pharmaceutical composition for treating alcoholism or states of alcoholism abuse. 2. A method as claimed in claim 1, wherein the compound of the formula I is selected from the following compounds: tert-butyl (2RS, 5SR)-1-{2-[3-(1-hydroxy-(RS)-3-ethylphenyl)ureido]acetyl}-5-phenylprolinate,  2-{3-{3-[2-((2S, 5R)-2-tert-butoxycarbonyl-5-phenyl-1-pyrrolidinyl)-2-oxoethyl]ureido}-phenyl}propionic acid,  (2RS, 5SR)-{3-{3-[2-(2-tert-butoxycarbonyl-5-phenyl-1-pyrrolidinyl)-2-oxoethyl]ureido}-phenylthio}acetic acid, (2R, 4R)-3-{3-[2-(4-tert-butoxycarbonyl-(2-fluoro-3-thiazolidinyl)-2-oxoethyl]ureido}-phenylacetic acid,  2-{3-{3-[2-((2R, 4R)-4-tert-butoxycarbonyl-2-(2-fluorophenyl)-3-thiazolidinyl)-2-oxoethyl]ureido} phenyl}propionic acid,  potassium (RS)-1-{3-{3-[2-((2R, 4R)-4-tert-butoxycarbonyl-2-phenyl-3-thiazolidinyl))-2-oxoethyl]ureido}phenyl}ethanesulphonate,  potassium (RS)-1-{3-{3-[2-((2S, 5R)-2-tert-butoxycarbonyl-5-phenyl-1-pyrrolidinyl)-2- oxoethyl]ureido}phenyl}ethanesulphonate,  potassium (2S, 5R)-1-{3-{3-[2-(2-tert-butoxycarbonyl-5-phenyl-1-pyrrolidinyl)-2-oxoethyl]ureido}phenylmethanesulphonate,  (2S, 5R)-3-{3-[2-2-tert-butoxycarbonyl-5-phenyl-1-pyrrolidinyl)-2-oxoethyl]ureido}benzoic acid,  (2RS, 5SR)-3-{3-{2-[2-tert-butoxycarbonyl-5-(2-fluorophenyl)-1-pyrrolidinyl]-2-oxoethyl}ureido}benzoic acid, (cis)-3-{3-[2-(2,5-diphenyl-1-pyrrolidinyl)-2-oxoethyl]-ureido}benzoic acid,  (2RS, 5SR)-3-{{2-[2-(2-hydroxyphenyl)-5-phenyl-1-pyrrolidinyl]-2-oxoureido}phenylacetic acid,  (2R, 4R)-3-{3-[2-(4-tert-butoxycarbonyl-2-phenyl-3-thiazolidinyl)-2-oxoethyl]ureido}phenylacetic acid,  (2R, 4R)-3-{3-[2-(4-tert-butoxycarbonyl-2-phenyl-3-thiazolidinyl)-2-oxoethyl]ureido}benzoic acid,  2-{3-{3-[2-((1RS, 2R, 4R)-4-tert-butoxycarbonyl-2-(2-fluorophenyl)-1-oxide-3-thiazolidinyl)-2-oxoethyl}ureido}phenyl}propionic acid,  (2R, 4R)-3-{3-[2-(4-tert-butoxycarbonyl-2-(2,3-difluorophenyl)-3-thiazolidinyl)-2-oxoethyl]ureido}phenylacetic acid, and  tert-butyl (2RS, 5SR)-1-{2-{3-[(E)-3-(1-(hydroxyimino)ethyl)phenyl]ureido}acetyl}-5-phenylprolinate. or their racemates or enantiomers, when they contain at least one asymmetric carbon atom , and salts thereof. 3. A method as claimed inclaim 1 wherein the compound of the formula I is 2-{3-{3-[2-((2R, 4R)-4-tert-butoxycarbonyl-2-(2-fluorophenyl)-3-thiazolidinyl)-2-oxoethyl]ureido}phenyl}propionic acid.