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

Conversion of the 2-(3-pyridyl)thiazolidine part of 4-[2-(3-pyridyl)th iazolidine-4-carbonyl]piperazine (YM461), which is a potent platelet-a ctivating factor (PAF) antagonist, to other rings was performed, and P AF antagonistic activities evaluated. The 2-(3-pyridyl)thiazolidine sk eleton, which exists as a mixture of cis and trans diastereomers, play ed an important role in the potency of PAF antagonism. in this study, new effective skeletons were not uncovered, however, 2-(4-pyridyl)thia zolidine-1-carboxamides (In and it) showed potent PAF antagonistic act ivities equal to the 3-pyridyl derivatives. From the results obtained for la, la(S), Ig and Ii, a is-(2R,4R)-2-(3-pyridyl)thiazolidine-4-car boxamide was assumed to be the active configuration for PAF antagonism .