title: 2-(3-Pyridyl)thiazolidine-4-carboxamides. 1. Novel orally active antagonists of platelet-activating factor (PAF).
abstract: 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.
authors.affiliation: Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nagaoka
authors.forename: H
authors.initials: H
authors.lastname: Hara
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.forename: M
authors.initials: M
authors.lastname: Takeuchi
authors.forename: A
authors.initials: A
authors.lastname: Matsuhisa
authors.forename: M
authors.initials: M
authors.lastname: Saito
authors.forename: T
authors.initials: T
authors.lastname: Yamada
authors.forename: K
authors.initials: K
authors.lastname: Tomioka
authors.forename: T
authors.initials: T
authors.lastname: Mase
mesh_terms: 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
chemical_list: D010879:Piperazines; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D013844:Thiazoles; D053778:Thiazolidines; C062972:YM 461; C068679:YM 264