SYNTHESIS AND PHARMACOLOGICAL EVALUATION OF -OXO-1,2,3-BENZOTRIAZIN-3-YL]-1H-PYRAZOLE-4-ACETIC ACID-DERIVATIVES

Several new ioxo-1,2,3-benzotriazin-3-yl]-1H-pyrazole-4-acetic acids a nd their ethyl ester derivatives were prepared. The compounds were tes ted for analgesic and antiinflammatory activities, acute toxicity, ulc erogenic effect, and as in vitro inhibitors of 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD), since it is claimed that the inhibition o f such an enzyme predicts in vivo antiinflammatory activity. Some comp ounds were more active than phenylbutazone in the phenylbenzoquinone a nd acetic acid peritonitis tests, and equiactive to the same drug in t he carrageenin paw edema test. All the compounds inhibited the 3 alpha -HSD, but no correlation was observed with the paw edema inhibition va lues. The compounds proved to possess marginal or no ulcerogenic effec t as well as low systemic toxicity. (C) 1998 Elsevier Science S.A. All rights reserved.