Synthesis and Antiplatelet Activities of N-Arylmethyl-3,4-dimethylpyranol[2,3-c]jpyrazol-6-one Derivatives

Abstract

A series of new 1- and 2-arylmethyl-3,4-dimethylpyrano [2,3-c] pyrazol-6-one derivatives were synthesized and examined for their antiplatelet activities. Some of these compounds showed significant inhibitory activities. Among them, 1 -phenyImethyI-3,4-dimethylpyrano[2,3-c]pyrazol-6 (1H)-one (4a), 2-(2'-methoxyphenyl)methyl-3,4-dimethyIpyrano [2,3-c] pyrazol-6(2H)-one (3e) and 2-(3'-methoxyphenyI)methyl-3,4-dimethylpyrano [2,3-c] pyrazol-6-(2H)-one (3f) were the most effective. These inhibitors acted in a concentration-dependent manner. The antiplatelet effect of compound 3f is due to the inhibition of thromboxane A2 formation and the blockade of thromboxane A2/prostaglandin endoperoxide receptor in washed rabbit platelets. © 1992, The Pharmaceutical Society of Japan. All rights reserved.