2-(3-Pyridyl)thiazolidine-4-carboxamide derivatives. II. Structure-activity relationships and active configuration of 2-(3-pyridyl)thiazolidine-4-carboxamides as platelet-activating factor receptor antagonists.

摘要

Conversion of the 2-(3-pyridyl)thiazolidine part of 1-(3-phenylpropyl)-4-[2-(3-pyridyl)thiazolidine-4-carbonyl]piperazine (YM461), which is a potent platelet-activating factor (PAF) antagonist, to other rings was performed, and PAF antagonistic activities evaluated. The 2-(3-pyridyl)thiazolidine skeleton, which exists as a mixture of cis and trans diastereomers, played an important role in the potency of PAF antagonism. In this study, new effective skeletons were not uncovered, however, 2-(4-pyridyl)thiazolidine-4-carboxamides (1n and 1z) showed potent PAF antagonistic activities equal to the 3-pyridyl derivatives. From the results obtained for 1a, 1a(S), 1g and 1i, a cis-(2R,4R)-2-(3-pyridyl)thiazolidine-4-carboxamide was assumed to be the active configuration for PAF antagonism.