Thromboxane A2 synthetase inhibitors with histamine H1-blocking activity: Synthesis and evaluation of a new series of indole derivatives

Article abstract of DOI:10.1248/cpb.43.1692

A novel series of N-substituted 3-(1H-imidazol-1-ylmethyl)indole carboxylic acid derivatives were prepared and evaluated for thromboxane A₂ (TXA₂) synthetase-inhibitory and histaminergic H₁-blocking activity. Among the compounds synthesized, indole-6-carboxylic acid derivatives showed higher activities than the other positional isomers of carboxylic acid. 1-[3-(4- Benzhydryl-1-piperazinyl)propyl]-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 H₁-blocking activity (IC₅₀ = 8 x 10^{- 9} M).