Design and Synthesis of Piperazinylpyridine Derivatives as Novel 5-HT1A Agonists/5-HT3 Antagonists for the Treatment of Irritable Bowel Syndrome (IBS)

Akira Asagarasu; Teruaki Matsui; Hiroyuki Hayashi; Satoru Tamaoki; Yukinao Yamauchi; Michitaka Sato

doi:10.1248/cpb.57.34

Regular Articles

Design and Synthesis of Piperazinylpyridine Derivatives as Novel 5-HT_1A Agonists/5-HT₃ Antagonists for the Treatment of Irritable Bowel Syndrome (IBS)

Akira Asagarasu, Teruaki Matsui, Hiroyuki Hayashi, Satoru Tamaoki, Yukinao Yamauchi, Michitaka Sato

著者情報

キーワード: structure–activity relationship, irritable bowel syndrome, serotonin receptor

ジャーナルフリー

2009 年 57 巻 1 号 p. 34-42

DOI https://doi.org/10.1248/cpb.57.34

詳細

抄録

We have prepared a series of piperazinylpyridine derivatives for the treatment of irritable bowel syndrome (IBS). These compounds, which were designed by pharmacophore analysis, bind to both serotonin subtype 1A (5-HT_1A) and subtype 3 (5-HT₃) receptors. The nitrogen atom of the isoquinoline, a methoxy group and piperazine were essential to the pharmacophore for binding to these receptors. We also synthesized furo- and thienopyridine derivatives according to structure–activity relationship analyses. Compound 17c (TZB-20810) had high affinities to these receptors and exhibited 5-HT_1A agonistic activity and 5-HT₃ antagonistic activity concurrently, and is a promising drug for further development in the treatment of IBS.

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