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 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.
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co. Ltd., Ibaraki, Japan.
T
T
Suzuki
H
H
Nagaoka
Y
Y
Kondo
T
T
Takahashi
M
M
Takeuchi
H
H
Hara
M
M
Saito
T
T
Yamada
K
K
Tomioka
M
M
Hamada
T
T
Mase
D000818:Animals; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology*; D011817:Rabbits; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry* / Q000494:pharmacology*; D053778:Thiazolidines
D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D013844:Thiazoles; D053778:Thiazolidines; C062972:YM 461