New μ-Opioid Receptor Agonists with Phenoxyacetic Acid Moiety

Susumu Sato; Teruo Komoto; Yoshihiko Kanamaru; Noriyuki Kawamoto; Tomomi Okada; Terumitsu Kaiho; Kinichi Mogi; Shinichi Morimoto; Norimitsu Umehara; Tadayuki Koda; Akira Miyashita; Takao Sakamoto; Yasuhiro Niino; Tetsuo Oka

doi:10.1248/cpb.50.292

Notes

New μ-Opioid Receptor Agonists with Phenoxyacetic Acid Moiety

Susumu Sato, Teruo Komoto, Yoshihiko Kanamaru, Noriyuki Kawamoto, Tomomi Okada, Terumitsu Kaiho, Kinichi Mogi, Shinichi Morimoto, Norimitsu Umehara, Tadayuki Koda, Akira Miyashita, Takao Sakamoto, Yasuhiro Niino, Tetsuo Oka

Author information

Susumu Sato
Central Research Laboratories SSP Co., Ltd.
Teruo Komoto
Central Research Laboratories SSP Co., Ltd.
Graduate School of Pharmaceutical Sciences, Tohoku University
Yoshihiko Kanamaru
Central Research Laboratories SSP Co., Ltd.
Noriyuki Kawamoto
Central Research Laboratories SSP Co., Ltd.
Tomomi Okada
Central Research Laboratories SSP Co., Ltd.
Terumitsu Kaiho
Central Research Laboratories SSP Co., Ltd.
Kinichi Mogi
Central Research Laboratories SSP Co., Ltd.
Shinichi Morimoto
Central Research Laboratories SSP Co., Ltd.
Norimitsu Umehara
Central Research Laboratories SSP Co., Ltd.
Tadayuki Koda
Central Research Laboratories SSP Co., Ltd.
Akira Miyashita
Central Research Laboratories SSP Co., Ltd.
Takao Sakamoto
Graduate School of Pharmaceutical Sciences, Tohoku University
Yasuhiro Niino
Central Research Laboratories SSP Co., Ltd.
Tetsuo Oka
Department of Pharmacology, School of Medicine, Tokai University

Keywords: μ-opioid receptor agonist, peripheral opioid analgesic, phenoxyacetic acid, 4-hydroxypiperidine

JOURNAL FREE ACCESS

2002 Volume 50 Issue 2 Pages 292-297

DOI https://doi.org/10.1248/cpb.50.292

Details

Abstract

New μ-opioid receptor (MOR) agonists containing 4-hydroxypiperidine, piperidine and piperazine moieties were synthesized and evaluated to find a peripheral opioid analgesic. Among the synthesized compounds, [2-[1-[3-(N,N-dimethylcarbamoyl)-3,3-diphenylpropyl]-4-hydroxypiperidin-4-yl]phenoxy]acetic acid (8: SS620) having phenoxyacetic acid and 4-hydroxypiperidine moieties showed the highest agonist potency on the MOR in an isolated guinea-pig ileum preparation, and it also had selectivity to the human MOR expressed in Chinese hamster ovary (CHO)-K1 cells compared with the same types of δ- and κ-opioid receptors (DOR and KOR). In addition, compound 8 showed a 10 times more potent MOR agonist activity than loperamide. Furthermore, compound 8 showed a peripheral analgesic activity in vivo screening on rat.

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