Synthesis and Evaluation of Novel Thiazolidine Derivatives as Thromboxane A2 Receptor Antagonists

Masakazu SATO; Yutaka KAWASHIMA; Jun GOTO; Yuuko YAMANE; Yoshiyuki CHIBA; Shuji JINNO; Mikio SATAKE; Takeshi IMANISHI; Chuzo IWATA

doi:10.1248/cpb.42.521

Synthesis and Evaluation of Novel Thiazolidine Derivatives as Thromboxane A₂ Receptor Antagonists

Masakazu SATO, Yutaka KAWASHIMA, Jun GOTO, Yuuko YAMANE, Yoshiyuki CHIBA, Shuji JINNO, Mikio SATAKE, Takeshi IMANISHI, Chuzo IWATA

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Keywords: thromboxane A₂, TXA₂, receptor, antagonist, thiazolidine, structure-activity relationship

JOURNAL FREE ACCESS

1994 Volume 42 Issue 3 Pages 521-529

DOI https://doi.org/10.1248/cpb.42.521

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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-11α, 9α-(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-ylmethyl]phenoxy-acetic acid (29d), which showed 10 times more potent TXA₂ receptor antagonist activity than 5a.

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