Thromboxane A2 Synthetase Inhibitors with Histamine H1-Blocking Activity : Synthesis and Evaluation of a New Series of Indole Derivatives

Shoji KAMIYA; Hiroshi MATSUI; Hiroaki SHIRAHASE; Shohei NAKAMURA; Katsuo WADA; Mamoru KANDA; Hisanobu SHIMAJI; Nobuharu KAKEYA

doi:10.1248/cpb.43.1692

Thromboxane A₂ Synthetase Inhibitors with Histamine H₁-Blocking Activity : Synthesis and Evaluation of a New Series of Indole Derivatives

Shoji KAMIYA, Hiroshi MATSUI, Hiroaki SHIRAHASE, Shohei NAKAMURA, Katsuo WADA, Mamoru KANDA, Hisanobu SHIMAJI, Nobuharu KAKEYA

Author information

Keywords: TXA₂ synthetase inhibitor, H₁-blocker, bronchoconstriction, structure-activity relationship, KY-234

JOURNAL FREE ACCESS

1995 Volume 43 Issue 10 Pages 1692-1695

DOI https://doi.org/10.1248/cpb.43.1692

Details

Abstract

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 positioal isomers of carboxylic acid. 1-[3-(4-Benzhyrdyl-1-piperazinyl)propyl]-3-(1H-imidazol-1-ylmethyl)-1H-indole-6-carboxylic acid (12) had the strongest thromboxane synthetase inhibitory activity (IC₅₀=5×10^-8M) and H₁-blocking activity (IC₅₀=8×10^-9M).

Corresponding author

Register with J-STAGE for free!