GB1492663A - 4-amino-3-pyrrole carboxamides - Google Patents

Abstract

1492663 Pyrrolidinecarboxamides GRUPPO LEPETIT SpA 4 Feb 1976 [20 Feb 1975] 7220/75 Heading C2C The invention comprises pyrrolidinecarboxamides of the Formula I wherein R is H, C 1-4 alkyl, benzyl or halobenzyl; R 1 is H, C 1-4 alkyl or phenyl optionally substituted 1 to 3 times by C 1-4 alkyl, C 1-4 alkoxy, benzyloxy, F, Cl, Br and OH; R 2 is H, C 1-4 alkyl, formyl, C 2-4 aliphatic carboxylic acyl, benzoyl, carbamoyl, phenylcarbamoyl, C 1-4 alkyl sulphonyl, benzenesulphonyl, toluenesulphonyl or phenacylsulphonyl; R 3 is H or C 1-4 alkyl; or R 2 and R 3 taken together represent C 2-4 alkylidene, benzylidene or halobenzylidene; R 4 and R 5 are H, C 2-4 alkyl or substituted phenyl, though not simultaneously H, or taken together with the nitrogen atom to which they are attached they may be dimethylamine or a 5-6 membered saturated heterocyclic ring optionally containing a further O or N atom and optionally substituted by 1 to 3 C 1-4 alkyl radicals or by a phenyl radical; R 6 is C 1-4 alkyl, and pharmaceutically acceptable acid addition salts thereof. The compounds are prepared either by reacting the appropriate 1 - R - 2 - R 6 - 5 R 1 - 4 - amino - 3 - pyrrolecarboxylic acids or acid addition salts thereof with phosgene and treating the resulting intermediates with amines of the formula HNR 4 R 5 or by reacting aminonitriles of the formula with compounds of the formula and, if desired, reacting the compounds of Formula I thus obtained in which R 2 and R 3 are both H, with C 1-4 alkyl halides, di(C 1-4 alkyl) sulphates, C 2-4 aliphatic acyl halides or anhydrides, benzoyl halides or anhydrides, benzene sulphenyl halides, C 1-4 alkyl sulphonyl halides, formic acid, alkali metal cyanates, phenyl isocyanate, acetaldehyde, propionaldehyde, butyraldehyde, isobutyraldehyde, acetone, ethyl methyl ketone, optionally substituted benzaldehydes. The following intermediates are also prepared: 5 - methyl - 7 - phenyl - 4H,6H - pyrrolo[3,4-d]- (1,3)oxazine - 2(1H),4 - dione; N,N - diethyl- 3 - (α - cyanobenzylamino) - crotonamide; 4- amino - 2 - methyl - 5 - phenyl - 3 - pyrrolecarboxylic acid and its hydrochloride and the hydrochloride of its ethyl ester; 3-amino-1-pchlorobenzyl - 2 - methyl - 5 - phenyl - 3 - pyrrole carboxylic acid hydrochloride; ethyl 4-(p-chlorobenzylideneamino) - 2 - methyl - 5 - phenyl- 3-pyrrolecarboxylate and ethyl 1-p-chlorobenzyl - 4 - (p - chlorobenzylideneamino) - 2- methyl - 5 - phenyl - 3 - pyrrolecarboxylate. Pharmaceutical compositions, suitable for oral, parenteral or rectal administration, contain the above compounds or acid addition salts thereof together with pharmaceutically acceptable carriers. The compounds possess antiinflammatory, antipyretic, CNS depressant and anti-hypertensive activities, and are also active as prostaglandin synthetase inhibitors.