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

共 50 条

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Suzuki, Shinya
Sugawara, Yuji
Tsuji, Riichiro
Tanimura, Ryuji
Kaneko, Chihiro
Yuzawa, Natsumi
Yagi, Mai
Kawai, Koji
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2019, 29 (03) : 515 - 515
[2] Syntheses of 10-oxo, 10α-hydroxy, and 10β-hydroxy derivatives of a potent κ-opioid receptor agonist, TRK-820
Horikiri, H
Hirano, N
Tanaka, Y
Oishi, J
Hatakeyama, H
Kawamura, K
Nagase, H
[J]. CHEMICAL & PHARMACEUTICAL BULLETIN, 2004, 52 (06) : 664 - 669
[3] Antipruritic activity of the κ-opioid receptor agonist, TRK-820
Togashi, Y
Umeuchi, H
Okano, K
Ando, N
Yoshizawa, Y
Honda, T
Kawamura, K
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Utsumi, J
Kamei, J
Tanaka, T
Nagase, H
[J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 2002, 435 (2-3) : 259 - 264
[4] Effect of TRK-820, a selective kappa opioid receptor agonist, an rat schizophrenia model
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Ikeda, Ken
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Kurokawa, Takahiro
Nakao, Kaoru
Mochizuki, Hidenori
Ichinose, Hiroshi
[J]. NEUROSCIENCE RESEARCH, 2008, 61 : S129 - S129
[5] Effects of TRK-820, a selective kappa opioid receptor agonist, on rat schizophrenia models
Yoshikawa, Satoru
Hareyama, Nana
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[J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 2009, 606 (1-3) : 102 - 108
[6] Potent antinociceptive effects of TRK-820, a novel κ-opioid receptor agonist
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Tajima, A
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Tseng, L
Nagase, H
[J]. LIFE SCIENCES, 1999, 65 (16) : 1685 - 1694
[7] Syntheses of potential metabolites of a potent κ-opioid receptor agonist, TRK-820
Kawamura, K
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Seki, C
Yoshizawa, K
Umeuchi, H
Nagase, H
[J]. CHEMICAL & PHARMACEUTICAL BULLETIN, 2004, 52 (06) : 670 - 674
[8] Pharmacological properties of TRK-820 on cloned μ-, δ- and κ-opioid receptors and nociceptin receptor
Seki, T
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Ide, S
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Minami, M
Nagase, H
Satoh, M
[J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 1999, 376 (1-2) : 159 - 167
[9] The effects of TRK-820, a κ-opioid agonist, on neuropathic pain
Hirakata, M
Takasaki, I
Suzuki, T
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Okano, K
Tanaka, T
Kuraishi, Y
Nagase, H
[J]. JAPANESE JOURNAL OF PHARMACOLOGY, 2002, 88 : 89P - 89P
[10] TRK-820, a selective κ-opioid agonist, produces potent antinociception in cynomolgus monkeys
Endoh, T
Tajima, A
Izumimoto, N
Suzuki, T
Saitoh, A
Suzuki, T
Narita, M
Kamei, J
Tseng, LF
Mizoguchi, H
Nagase, H
[J]. JAPANESE JOURNAL OF PHARMACOLOGY, 2001, 85 (03): : 282 - 290

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