Patent GB-1356118-A (GB)
Title: 1-3-cyano-3,3-diphenylpropyl-4-phenylpiperidine-4-carboxylic acid derivatives
IPC: C07D211/64
Filed: 1970-12-16
Abstract: 1356118 4 - Phenylpiperidine - 4 - carboxylic derivatives G D SEARLE & CO 13 Dec 1971 [16 Dec 1970] 57390/71 Divided out of 1356117 Heading C2C Novel compounds of the formula and acid addition salts thereof, wherein Q is chlorine, aryloxy, heteroaryloxy, -NHNRR 1  wherein R and R 1  are each hydrogen, alkyl, aryl alkanoyl or toluenesulphonyl, and in addition, when R is hydrogen, R 1  is 1-(3-cyano-3,3-diphenyl - propyl) - 4 - phenylpiperidine - 4- carbonyl, or R and R 1  together represent wherein X 1  is sulphur, oxygen, -NH-, or -(CH 2 ) n - (n is 0, 1 or 2) and R 2  is H or one or more methyl substituents; or Q is wherein R 3  is alkyl, aryl, trifluoromethyl or 1- (3 - cyano - 3,3 - diphenylpropyl) - 4 - phenylpiperidine-4-carbonyloxy radical; or Q is -SX 2  where X 2  is alkyl, aralkyl, heteroaralkyl, aryl or heteroaryl; or Q is -NR 4 R 5  wherein R 4  and R 5  each represent alkoxyalkyl, cycloalkyl, aryl or heteroaryl, R 4  may additionally be hydrogen, or -NR 4 R 5  represents succinimido, glutarimido, phthalimido or maleimido; or Q is X 3 -alkylene-Y wherein X 3  is oxygen, sulphur or -NH-, Y is -NR 6 R 7  wherein R 6  and R 7  each represent alkyl or aralkyl or -NR 6 R 7  represents cuccinimido, glutarimido, phthalimido or maleimido or Y is a radical of the formula wherein R 2  and n have the above significance and X 4  is oxygen, sulphur, -NH- or -CH 2 -, or Y is a radical of the formula wherein X 5  is oxygen, sulphur or -NH-, or Y is cyano, alkanoyl, aroyl, heteroaroyl, carbalkoxy or heteraryl, and in addition, when X 3  is -NH-, Y is aryl, are prepared (a) in the case where Q is other than a chlorine atom by reacting Q-H with a compound of the first formula above wherein Q is chlorine or hydroxy ; and (b) in the case where Q is -O-alkylene-Y by reacting a compound of the first formula above wherein Z is hydroxy with Halalkylene-Y wherein Y has the above significance and Hal is bromine or chlorine. The term " aryl " means unsubstituted and substituted aryl (a number of suitable substitutents are specified) and " heteroaryl" means unsubstituted radicals such as pyridine, quinoline, isoquinoline, pyrimidine and pyrazine and the corresponding radicals substituted by one or more methyl radicals. The compounds of the first general formula above wherein (a) Z is chlorine are prepared by treating the corresponding compounds wherein Z is hydroxy with thionyl chloride, (b) Z is -NHNH 2  by reacting an alkyl ester of an acid of the first formula above wherein Z is OH with lithium hydrazide, and (c) Z is (R 8  is alkyl, aryl or CF), by reacting a compound of the first formula above wherein Z is OH with the anhydride  Therapeutic compositions contain as the active ingredient the novel compounds of the first formula above. The compositions have antidiarrheal, analgesic, anti-protozoal, anti-bacterial, anti-algal, anti-fungal and anthelmintic activity and are also useful for counteracting the withdrawal symptoms of substances which produce chronic, psychotropic drug intoxication and may be administered in the form of tablets, lozenges, capsules, dragees, pills, powders, solutions, suspensions or syrups.