Patent GB-1392810-A (GB)
Title: Pharmaceutical compositions containing thioamides and nitriles
IPC: C07D211/60
Filed: 1971-10-29
Abstract: 1392810 Thioamides and nitriles of piperidine and tetrahydropyridine and their pharmaceutical compositions JOHN WYETH & BRO Ltd 20 Oct 1972 [29 Oct 1971] 50431/71 Heading C2C The invention comprises compounds of the general Formula I and acid addition salts thereof wherein R<SP>1</SP> is hydrogen or an optionally substituted alkyl or aralkyl group; the dotted line represents an optional double bond; X is hydrogen, a group SR<SP>3</SP> where R<SP>3</SP> is H or an optionally substituted alkyl, aryl or aralkyl group or an optionally etherified or esterified hydroxy group; Y is CN or CSNHR<SP>3</SP> where R<SP>2</SP> is H or an optionally substituted alkyl group and Z is a radical of Formula Ic or Id wherein R is H or an optionally substituted alkyl or aralkyl radical or carbonylic acyl group provided that (a) when Formula I contains a double bond in the ring X is absent, (b) when X is absent or H and R<SP>1</SP> is H then Y is CSNH 2  and R is other than H and (c) when Y is CN and X is present then X is the group SR<SP>3</SP> where R<SP>3</SP> is as defined above other than hydrogen. The invention also comprises pharmaceutical compositions comprising a compound of Formula I or an acid addition salt thereof together with a pharmaceutically acceptable carrier, the compositions having anti-ulcer activity for oral administration and optionally also containing one or more antacid ingredients. Compounds of Formula I in which Y represents CSNHR<SP>2</SP> wherein R<SP>2</SP> is as defined above may be prepared by a compound of Formula I in which Y represents CN with H 2 S, optionally in the presence of a primary amine RNH 2  when R<SP>2</SP> is to be other than H, or if R<SP>2</SP> is to be other than H by alkylation of a compound of Formula I in which Y is CSNHR<SP>2</SP> and R<SP>2</SP> is hydrogen. Compounds of Formula I in which Y is CSNH 2  and X is absent or hydrogen may be prepared by treating a corresponding compound in which Y is CN with a thioamide of formula R<SP>4</SP>CSNH 2  where R<SP>4</SP> is alkyl. Compounds of Formula I in which Y is CSNHR<SP>2</SP> and X is absent or hydrogen may be prepared by reacting a corresponding compound in which Y is CONHR<SP>2</SP> with P 2 S 5 . Compounds of Formula I in which Y is CSNHR<SP>2</SP> may be prepared by reacting a corresponding compound in which Y is with a primary amine of formula R<SP>2</SP>NH 2 . Compounds of Formula I wherein Y is CN and X is SR<SP>3</SP> may be prepared by reacting a corresponding unsaturated compound of Formula I wherein X is absent with a compound of formula R<SP>3</SP>SH wherein R<SP>3</SP> is an optionally substituted alkyl, aryl or aralkyl radical. Compounds of Formula I in which Y is CN, R and R<SP>1</SP> are independently optionally substituted alkyl or aralkyl, X is absent and the ring is unsaturated may be prepared by reduction of a compound of Formula XI and XIa in which R and R<SP>1</SP> are as defined and A(-) is an anion, e.g. with sodium borohydride. Compounds of Formula I wherein Y is CN and R is H, alkyl or aralkyl may be prepared by cyclization of an open chain compound of Formula XII in the presence of a basic condensing agent. Compounds of Formula I in which X is hydrogen or is absent, Y is CN and R is other than hydrogen may be prepared by alkylating, aralkylating or acylating a corresponding compound in which R is hydrogen. 3 - Cyano - 4 - imino - piperidine is prepared by reaction of di(2-cyanoethyl)amine with sodium in the presence of naphthalene and is N-acylated with acetic anhydride to obtain 1-acetyl-3-cyano-4-iminopiperidine which is in turn hydrolysed to obtain 1-acetyl-3-cyano-4- piperidine. N - (# - Cyanoethyl) - N - butan - 3 - one benzylamine is prepared by reaction of #-cyanoethylbenzylamine with paraformaldehyde and acetone.