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.