Discovery of highly selective κ-opioid receptor agonists: 10α-Hydroxy TRK-820 derivatives

被引：8

作者：

Suzuki, Shinya ^{[1
]}

Sugawara, Yuji ^{[1
]}

Tsuji, Riichiro ^{[1
]}

Tanimura, Ryuji ^{[1
]}

Kaneko, Chihiro ^{[1
]}

Yuzawa, Natsumi ^{[1
]}

Yagi, Mai ^{[1
]}

Kawai, Koji ^{[1
]}

机构：

[1] Toray Industries Ltd, Pharmaceut Res Labs, 6-10-1 Tebiro, Kamakura, Kanagawa 2488555, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2017年 / 27卷 / 16期

关键词：

mu-Opioid receptor; kappa-Opioid receptor; Analgesic; Antipruritic; 4,5-Epoxymorphinan; TRK-820; DESIGN; ANTAGONISTS; MORPHINE;

D O I：

10.1016/j.bmcl.2017.06.017

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

kappa-Opioid receptor agonists with high selectivity over the mu-opioid receptor are attractive targets in the development of drugs for pain and pruritus. We previously reported the synthesis of 10 alpha-hydroxy TRK-820 (1). In this study, we elucidated the biological properties of 1 and optimized its 6-acyl unit by modifying our synthetic route. Among the 10 alpha-hydroxy TRK-820 derivatives prepared, 26 showed the most potent kappa-opioid agonist activity (EC50= 0.00466 nM) and excellent selectivity and 22 was the most kappa-selective agonist. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：3920 / 3924

页数：5

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