Synthesis of the Selective 5-Hydroxytryptamine 4 (5-HT4) Receptor Agonist (+)-(S)-2-Chloro-5-methoxy-4-[5-(2-piperidylmethyl)-1, 2, 4-oxadiazol-3-yl]aniline

Takeshi SUZUKI; Kiyoshi IWAOKA; Naoki IMANISHI; Yukinori NAGAKURA; Kenji MIYATA; Hideaki NAKAHARA; Mitsuaki OHTA; Toshiyasu MASE

doi:10.1248/cpb.47.120

Synthesis of the Selective 5-Hydroxytryptamine 4 (5-HT₄) Receptor Agonist (+)-(S)-2-Chloro-5-methoxy-4-[5-(2-piperidylmethyl)-1, 2, 4-oxadiazol-3-yl]aniline

Takeshi SUZUKI, Kiyoshi IWAOKA, Naoki IMANISHI, Yukinori NAGAKURA, Kenji MIYATA, Hideaki NAKAHARA, Mitsuaki OHTA, Toshiyasu MASE

Author information

Takeshi SUZUKI
Kiyoshi IWAOKA
Naoki IMANISHI
Yukinori NAGAKURA
Kenji MIYATA
Hideaki NAKAHARA
Mitsuaki OHTA
Toshiyasu MASE
Author's Organization：
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.,
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.,
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.,
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.,
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.,
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.,
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.,
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.,

Keywords: 5-hydroxytryptamine 4 agonist, 1, 2, 4-oxadiazole, S isomer

JOURNAL FREE ACCESS

1999 Volume 47 Issue 1 Pages 120-122

DOI https://doi.org/10.1248/cpb.47.120

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Abstract

In a search for novel 5-hydroxytryptamine 4 (5-HT₄) agonists focusing on the linker group of benzamide derivatives, 2-chloro-5-methoxy-4-[5-(2-piperidylmethyl)-1, 2, 4-oxadiazol-3-yl]aniline (2) was prepared and its optical isomers were separated. The S isomer 2(S) showed high affinity for the human 5-HT₄ receptor without affinity for the human 5-HT₃ receptor, and potent 5-HT₄ agonistic activity in longitudinal muscle myenteric plexus (LMMP) preparations of guinea pig ileum. The R isomer 2(R) showed opposite selectivity. As a result of other receptor binding studies, 2(S) (YM-53389) was shown to be a highly selective 5-HT₄ agonist.

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