Neue 1-Aroylbenzimidazole und 1-Aroylbenzotriazole

摘要

1,209,533. 1 - Aroyl - benzimidazoles and -benzotriazoles. CHAS PFIZER & CO. Inc. 12 June, 1968 [20 March, 1968], No. 28035/68. Heading C2C. Novel 1-aroyl-benzimidazoles and -benzotriazoles having one of the following formulµ wherein R1 is CH 3 , COOH, Cl or Br; R2 is CF 3 , NHCOCF 3 or CH 2 CH 2 COOH; R3 is H, Cl or Br; R4 is CH 3 or OCH 3 ; R5 is H or CH 3 ; R6 is H, COOH, N(CH 3 ) 2 , OCH 2 COOH or OCH 2 - COOCH 2 C 6 H 5 , provided that R4 is CH 3 O, when R6 is H; R7 is CF 3 or 2-pyridyl; R8 is Br, Cl or OCH 2 COOH; R9 and R9' are each CH 3 or one is H and the other is Br or Cl; and R10 is R11- phenyl (in which R11 is H, Cl or OCH 2 COOH), p - dimethylaminophenyl, 3,4,5 - trimethoxyphenyl or 2,6-dimethoxyphenyl, are prepared (a) by reaction of the appropriate benzimidazole or benzotriazole with a suitable aroyl halide in an inert anhydrous solvent, in the presence of an organic base; (b) when the product contains a carboxy group in the aroyl portion of the molecule, by aroylation of the benzimidazole with the benzyl ester of the aroyl halide, followed by hydrogenolysis of the resulting benzyl ester; or (c) when R1 is COOH or R2 is CH 2 CH 2 - COOH, by aroylation of the benzyl ester of the carboxy-imidazole or 2-(21-carboxyethyl)-benzimidazole, respectively, followed by hydrogenolysis of the resulting benzyl ester. 2 - Trifluoroacetamido - 5 - chloro -, - 4 - or 5 - bromo -, - 5 - carboxy -, and - 4 - or 5 - methyl-benzimidazoles are prepared by reaction of the appropriate 2-amino-benzimidazole with trifluoroacetic anhydride. 2-Trifluoromethyl-5- carboxy-benzimidazole is prepared by reaction of 3,4-diaminobenzoic acid with trifluoroacetic acid. Benzyl (4 - chlorocarbonylphenoxy) acetate is prepared by reaction of p-hydroxybenzoic acid with isobutylene in the presence of concentrated sulphuric acid, reaction of the resulting t-butyl p-hydroxybenzoate with benzyl bromoacetate in the presence of sodium hydride, followed by trifluoroacetic acid, and treatment of the benzyl (4-carboxy-phenoxy)-acetate so obtained with thionyl chloride. The corresponding 2- and 3-chloro derivatives are prepared analogously. 2 - (21 - Carbobenzoxyethyl) - 5 - chlorobenzimidazole is prepared by reaction of 2,(21- carboxyethyl) - 5 - chlorobenzimidazole with benzyl alcohol in the presence of thionyl chloride. 2 - (21 - Carbobenzoxyethyl) - 5 - carbobenzoxybenzimidazole is prepared analogously. Pharmaceutical compositions having antiinflammatory activity comprise, as active ingredient, a 1-aroyl-benzimidazole or -benzotriazole of one of the above formulµ, together with a pharmaceutically acceptable carrier, and may be administered orally or parenterally.