2-(3-Pyridyl)thiazolidine-4-carboxamides. 1. Novel orally active antagonists of platelet-activating factor (PAF).
In a search for novel platelet-activating factor (PAF) antagonists, we found that 1-(3-phenylpropyl)-4-[2-(3-pyridyl)thiazolidine-4-carbonyl] piperazine (3x) showed in vitro and in vivo PAF-antagonistic activities. Introduction of functional groups at the benzylic methylene carbon of 3x afforded some compounds with more potent PAF-antagonistic activity than 3x. Among them 1-(3-methyl-3-phenylbutyl)-4-[2-(3-pyridyl) thiazolidine-4-carbonyl]-piperazine fumarate (3al, YM264) was found to be one of the most potent PAF antagonists.
Nagaoka
H
H
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
Hara
H
H
Suzuki
T
T
Takahashi
T
T
Takeuchi
M
M
Matsuhisa
A
A
Saito
M
M
Yamada
T
T
Tomioka
K
K
Mase
T
T
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D006168:Guinea Pigs; D006400:Hematocrit; D006801:Humans; D051379:Mice; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*; D053778:Thiazolidines
D010879:Piperazines; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D013844:Thiazoles; D053778:Thiazolidines; C062972:YM 461; C068679:YM 264