title: Synthesis and evaluation of novel thiazolidine derivatives as thromboxane A2 receptor antagonists.
abstract: A series of 3-benzoyl or 3-phenylsulfonyl-2-substituted thiazolidine derivatives were synthesized, and evaluated for their thromboxane A2 (TXA2) receptor-antagonizing effect on (15S)-15-hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5(Z),13(E)-dienoic acid (U-46619)-induced aggregation of rabbit platelet-rich plasma (PRP). A simple 2-aryl-thiazolidine derivative, 3-benzoyl-2-(4-hydroxy-3-methoxyphenyl)thiazolidine (5a), showed mild TXA2 receptor antagonist activity. Modification of 5a led to 2-chloro-4-[3-(4-chlorophenylsulfonyl)thiazolidin-2-ylmet hyl]phenoxyacetic acid (29d), which showed 10 times more potent TXA2 receptor antagonist activity than 5a.
authors.affiliation: Research Center Taisho Pharm. Co., Ltd., Saitama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Sato
authors.forename: Y
authors.initials: Y
authors.lastname: Kawashima
authors.forename: J
authors.initials: J
authors.lastname: Goto
authors.forename: Y
authors.initials: Y
authors.lastname: Yamane
authors.forename: Y
authors.initials: Y
authors.lastname: Chiba
authors.forename: S
authors.initials: S
authors.lastname: Jinno
authors.forename: M
authors.initials: M
authors.lastname: Satake
authors.forename: T
authors.initials: T
authors.lastname: Imanishi
authors.forename: C
authors.initials: C
authors.lastname: Iwata
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011817:Rabbits; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D013928:Thromboxane A2 / Q000378:metabolism*
chemical_list: D010975:Platelet Aggregation Inhibitors; D017482:Receptors, Thromboxane; D013844:Thiazoles; D013928:Thromboxane A2