Synthesis and biological evaluation of aryl isoxazole derivatives as metabotropic glutamate receptor 1 antagonists: A potential treatment for neuropathic pain

被引：8

作者：

Cho, Gyeong Hi ^{[1
,2
]}

Kim, TaeHun ^{[1
,3
]}

Son, Woo Seung ^{[1
,2
]}

Seo, Seon Hee ^{[1
]}

Min, Sun-Joon ^{[1
]}

Cho, Yong Seo ^{[1
]}

Keum, Gyochang ^{[1
]}

Jeong, Kyu-Sung ^{[2
]}

Koh, Hun Yeong ^{[4
]}

Lee, Jiyoun ^{[5
]}

Pae, Ae Nim ^{[1
,3
]}

机构：

[1] Korea Inst Sci & Technol, Brain Sci Inst, Ctr Neuromed, Seoul 130650, South Korea

[2] Yonsei Univ, Dept Chem, Seoul 120749, South Korea

[3] Korea Univ Sci & Technol, Biol Chem, Taejon 305350, South Korea

[4] Inha Univ, Dept Chem, Inchon 402751, South Korea

[5] Sungshin Univ, Dept Global Med Sci, Seoul 142732, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2015年 / 25卷 / 06期

关键词：

mGluR1; antagonist; Metabotropic glutamate receptor; Neuropathic pain; Schizophrenia; Aryl isoxazole; MGLUR1; ANTAGONISTS; RAT; DISORDERS; PROFILE; PHARMACOLOGY; KNOCKDOWN; ALLODYNIA; DISCOVERY; PROSPECTS; BRAIN;

D O I：

10.1016/j.bmcl.2015.01.035

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Glutamate is the major excitatory neurotransmitter and known to activate the metabotropic and ionotropic glutamate receptors in the brain. Among these glutamate receptors, metabotropic glutamate receptor 1 (mGluR1) has been implicated in various brain disorders including anxiety, schizophrenia and chronic pain. Several studies demonstrated that the blockade of mGluR1 signaling reduced pain responses in animal models, suggesting that mGluR1 is a promising target for the treatment of neuropathic pain. In this study, we have developed mGluR1 antagonists with an aryl isoxazole scaffold, and identify several compounds that are orally active in vivo. We believe that these compounds can serve as a useful tool for the investigation of the role of mGluR1 and a promising lead for the potential treatment of neuropathic pain. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：1324 / 1328

页数：5

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