Cross P E, Dickinson R P, Parry M J, Randall M J
J Med Chem. 1986 Mar;29(3):342-6. doi: 10.1021/jm00153a007.
The preparation of a series of 3-(1H-imidazol-1-ylmethyl)-1H-indole-1-alkanoic acids is described. Several compounds were found to be more potent thromboxane synthetase inhibitors than the corresponding analogues lacking an acidic substituent. In the cases examined, compounds had no significant activity against PGI2 synthetase or cyclooxygenase, and introduction of the carboxylic acid substituent led to a reduction in activity against adrenal steroid 11 beta-hydroxylase. Compound 21 strongly inhibited thromboxane formation after iv administration to anesthetized rabbits and oral administration to conscious dogs. The compound had a long duration of action, and marked inhibition of thromboxane production was observed 15 h after oral administration of 1 mg/kg to conscious dogs.
描述了一系列3-(1H-咪唑-1-基甲基)-1H-吲哚-1-链烷酸的制备方法。发现几种化合物作为血栓素合成酶抑制剂比相应的缺乏酸性取代基的类似物更有效。在所研究的情况下，化合物对前列环素合成酶或环氧化酶没有显著活性，并且羧酸取代基的引入导致对肾上腺类固醇11β-羟化酶的活性降低。化合物21在静脉注射给麻醉兔和口服给清醒犬后强烈抑制血栓素的形成。该化合物作用持续时间长，在给清醒犬口服1mg/kg后15小时观察到对血栓素产生的显著抑制。
