Selective Thromboxane Synthetase Inhibitors. 2. 3-(1H-Imidazol-1-ylmethyl)-2-methyl-1H-indole-1-propanoic Acid and Analogues

Article abstract of 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 11β-hydroxylase.Compound 21 strongly inhibited thromboxane formation after iv administration to anesthetized rabbitsand 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.