THROMBOXANE A(2) SYNTHETASE INHIBITORS WITH HISTAMINE H-1-BLOCKING ACTIVITY - SYNTHESIS AND EVALUATION OF A NEW SERIES OF INDOLE-DERIVATIVES

A novel series of N-substituted 3-(1H-imidazol-1-ylmethyl)indole carbo xylic acid derivatives were prepared and evaluated for thromboxane A(2 ) (TXA(2)) synthetase-inhibitory and histaminergic H-1-blocking activi ty. Among the compounds synthesized, indole-6-carboxylic acid derivati ves showed higher activities than the other positional isomers of carb oxylic acid, -3-(1H-imidazol-1-ylmethyl)-1H-indole-6-carboxylic acid ( 12) had the strongest thromboxane synthetase inhibitory activity (IC50 = 5 x 10(-8) M) and H-1-blocking activity (IC50 = 8 x 10(-9) M).