Patent GB-1396748-A (GB)
Title: 4-4-biphenylyl - butyramides
IPC: C07D307/33
Filed: 1972-08-18
Abstract: 1396748 4 - (4 - Biphenylyl) - butyric acid amides DR KARL THOMAE GmbH 18 Aug 1972 [20 Aug 1971 (3)] 38712/72 Heading C2C The invention comprises 4-(4-biphenylyl)- butyric acid amides of the Formula I wherein A is R 1  is halogen, H, NO 2 , NH 2  or CN with the proviso that where A is -CH 2 CH 2 CH 2 - R 1  is halogen; R 2  is H or halogen; and R 3  and R 4  each are H, C 1-5  alkyl optionally substituted by H or C 1 -alkoxy, or phenyl optionally substituted by halogen, OH, CF 3 , C 1 -alkyl or C 1 -alkoxy; or R 3  and R 4  together with the nitrogen atom to which they are attached form a 1-pyrrolidinyl, piperidino, morpholino or 1-piperazinyl group each of which may be substituted by C 1 -alkyl, and acid addition salts of these compounds which contain basic nitrogen atoms. The compounds are prepared by reacting compounds of the formula wherein A is -CHOH-CH 2 CH 2 -, X is OR, where R is alkyl, aryl or aralkyl, and A is -COCH 2 CH 2 - or -CH 2 CH 2 CH 2 -, X is O-CO-OR, O-CO-R or OR or halogen or OH with the proviso that X may not be OH unless A is CH 2 CH 2 CH 2  with compounds of the formula HNR 3 R 4 , and, if necessary, removing protecting groups from any protected amino groups present. Compounds in which A is -COCH 2 CH 2 - may also be prepared by reacting the corresponding 5-(4-biphenylyl)-2(3H)- furanones, obtained by treating the appropriate 4 - (4 - biphenylyl) - 4 - oxobutyric acids with acetic anhydride; with compounds of the formula HNR 3 R 4 , or by reducing the corresponding 4 - (4 - biphenylyl) - 4 - oxocrotonic acid amides. Compounds in which A is may also be made by reducing compounds in which A is .COCH 2 CH 2 , or by reducing a mixture of such compounds with the corresponding 1 - R 3  - 5 - (4 - biphenylyl) - 5 - hydroxy - 2- pyrrolidinones, or by reducing the corresponding 4-(4-biphenylyl)-4-oxocrotonic acid amides or 4- (4-biphenylyl)-4-hydroxy-crotonic acid amides, or by reacting the appropriate γ-(4-biphenylyl)- γ-butyrolactones with compounds of the formula NHR 3 R 4 . Compounds in which A is may also be obtained by reducing compounds in which A is -COCH 2 CH 2  or Compounds in which R 1  is NH 2  may be prepared by reducing the corresponding compounds of Formula I in which R 1  is NO 2 . 4 - (2<SP>1</SP>,3<SP>1</SP> - Dichloro - 4 - biphenylyl) - butyric acid chloride is obtained by reacting the acid with thionyl chloride. 4 - (2<SP>1</SP> - Fluoro - 4 - biphenylyl) - 4 - oxo - N- propylcrotonamide is obtained by the mixed anhydride of the acid with ethyl chloroformate with propylamine. 4 - (2<SP>1</SP> - Nitro - 4 - biphenylyl) - 4 - oxobutyric acid benzoic anhydride is made by reacting the acid with benzoyl chloride.  5 - (2<SP>1</SP> - Fluoro - 4 - biphenylyl) - 1 - ethyl - 5- hydroxy-2-pyrrolidinone is obtained by reacting γ - (4<SP>1</SP> - fluoro - 4 - biphenylyl)-γ-butyrolactone with ethylamine. Pharmaceutical compositions, suitable for oral, parenteral or rectal administration, contain the above novel compounds or pharmaceutically acid addition salts of those compounds having basic nitrogen atoms in association with pharmaceutical carriers or diluents. The compounds possess antiphlogistic activity.