Patent GB-1319040-A (GB)
Title: 2,2,-diaryl-4-4-aryl-4-hydroxy-piperidino butyramides
IPC: C07D211/74
Filed: 1971-05-25
Abstract: 1319040 4 - (4 - Hydroxypiperidino)butyramides JANSSEN PHARMACEUTICA NV 25 May 1971 [1 June 1970 30 March 1971] 16839/71 Heading C2C  The invention comprises novel 4-(4-hydroxypiperidino)butyramides of the Formulµ and therapeutically acceptable addition salts thereof wherein R is H or CH 3 , Ar 1  is phenyl or halophenyl, Ar 2  is phenyl or halophenyl, R 5  is H or CH 3  and -N=2 is 1-pyrrolidinyl, piperidino optionally substituted by CH 3 , morpholino, 2,6-di-(C 1-6  alkyl)morpholino, N(CH 2 CH = CH 2 ) 2 , -NR 3 R 4  in which R 3  is C 1-6  alkyl or benzyl and R 4  is C 1-6  alkyl; -N=Z 1  is NH 2  or -NH- (C 1-6  alkyl); -N=Z 2  is -N(C 1-6  alkyl) 2 ; and Ar 3  is phenyl or substituted phenyl; provided that when R 5  is CH 3  then -N = Z is other than N(CH 2 CH=CH 2 ) 2 ; and their preparation. The compounds are prepared by reacting the appropriate 4-(Ar 3 )-4-hydroxy-3R-piperidines with compounds of the formula or with compounds of the formula or with tetrahydrofuran derivatives of the formulµ wherein AN is a suitable anion, which are obtained by reacting compounds of the formula Ar 1  Ar 2 C.(COCl)CH 2 CH 2 Br with compounds of the formula HN=Z 1  or H-N=Z, or when R<SP>5</SP> is CH 3 , by reacting with the appropriate acids of the formula HAN. Other intermediates and starting materials are: 4 - bromo - 2,2 - diphenylbutyric acid, and the acid chloride thereof, 2,2-bis-(p-fluorophenyl)acetonitrile, 4 - bromo - 2,2 - bis-(pfluorophenyl)butyronitrile, 2,2 - bis - (p - fluorophenyl) - 4 - hydroxybutyric acid γ - lactone, 4 - bromo - 2,2 - bis - (p - fluorophenyl)butyric acid and the acid chloride thereof. 4-bromo-2- (p - fluorophenyl) - 2 - phenylbutyrylchloride, 4 - chloro - 2,2 - diphenylbutyramide, tetrahydro - 4 - methyl - 3,3 - diphenyl - 2 - furanimine hydrochloride, 2 - bromo - 2 - (p - fluorophenyl)acetonitrile, 3 - cyano - 2 - methyl- 3,3 - diphenylpropionic acid chloride, N-(tetrahydro - 3,3 - diphenyl - 2 - furylidene)methylamine, 4 - chloro - N - methyl - 2,2 - diphenylbutyramide, 4 - chloro - N - methyl - 2,2- bis - (p - fluorophenyl)butyramide, 4 - chloro- N - ethyl - 2,2 - diphenylbutyramide, 4- chloro- N - methyl - 2 - (p - fluorophenyl) - 2 - phenylbutyramide, 4 - chloro - 2,2 - bis - (p - fluorophenyl)butyramide, 4 - chloro - 2 - (p - fluorophenyl) - 2 - phenylbutyramide, N,N - dimethyl - 2,2 - diphenyl - 4 - pentenamide, 1 - (2,2 - diphenyl - 4 - pentenoyl)pyrrolidine, 4 - hydroxy - N, N - dimethyl - 2,2 - diphenylbutyramide, 4 - chloro - N,N - dimethyl - 2,2- diphenylbutyramide, methyl N,N - bis - [2- (methoxycarbonyl)ethyl]carbamate, dimethyl 4 - oxo - 1,3 - piperidinedicarboxylate, dimethyl- 3 - methyl - 4 - oxo - 1,3 - piperidinedicarboxylate, methyl - 3 - methyl - 4 - oxo - 1 - piperidinecarboxylate, 1 - ethoxy - carbonyl - 4 - (4- bromophenyl) - 4 - hydroxypiperidine, 1- ethoxycarbonyl - 4 - hydroxy - 4 - (3,4,5 - trimethylphenyl)piperidine, methyl 4 - (p - chlorophenyl) - 4 - hydroxy - 3 - methyl - 1 - piperidinecarboxylate, methyl 4 - (4 - chloro - 3 - trifluoromethylphenyl) - 4 - hydroxy - 3 - methylpiperinecarboxylate, 4 - (4 - bromophenyl) - 4- hydroxypiperidine, 4 - hydroxy - 4 - (3,4,5- trimethylphenyl)piperidine, α,dl - 4 - (p - chlorophenyl) - 3 - methyl - 4 - piperidinol, α-(+) - 4- (4 - chloro - 3 - trifluoromethylphenyl) - 3- methyl - 4 - piperidinol hydrochloride, 4- hydroxy - 4 - (3,5 - dimethylphenyl)piperidine, α - (+) - 3 - methyl - 4 - (p - tolyl) - 4 - piperidinol and α - (+) - 4 - (p - methoxyphenyl)- 3-methyl-4-piperidinol. Pharmaceutical compositions, suitable for oral or parenteral administration, contain the above novel compounds and pharmaceutically acceptable diluents or carriers. The compounds possess anti-diarrheal and analgesic activities.