Synthesis and evaluation of novel thiazolidine derivatives as thromboxane A2 receptor antagonists.
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.
Sato
M
M
Research Center Taisho Pharm. Co., Ltd., Saitama, Japan.
Kawashima
Y
Y
Goto
J
J
Yamane
Y
Y
Chiba
Y
Y
Jinno
S
S
Satake
M
M
Imanishi
T
T
Iwata
C
C
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*
D010975:Platelet Aggregation Inhibitors; D017482:Receptors, Thromboxane; D013844:Thiazoles; D013928:Thromboxane A2