Cho, Gyeong Hi Kim, TaeHun Son, Woo Seung Seo, Seon Hee Min, Sun-Joon Cho, Yong Seo Keum, Gyochang Jeong, Kyu-Sung Koh, Hun Yeong Lee, Jiyoun Pae, Ae Nim 2024-01-20T07:32:14Z 2024-01-20T07:32:14Z 2021-09-04 2015-03-15 0960-894X https://pubs.kist.re.kr/handle/201004/125663 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. English Pergamon Press Ltd. MGLUR1 ANTAGONISTS RAT DISORDERS PROFILE PHARMACOLOGY KNOCKDOWN ALLODYNIA DISCOVERY PROSPECTS BRAIN Synthesis and biological evaluation of aryl isoxazole derivatives as metabotropic glutamate receptor 1 antagonists: A potential treatment for neuropathic pain Article 10.1016/j.bmcl.2015.01.035 1 Bioorganic & Medicinal Chemistry Letters, v.25, no.6, pp.1324 - 1328 Bioorganic & Medicinal Chemistry Letters 25 6 1324 1328 scie scopus 000350696000031 2-s2.0-84923802343 Chemistry, Medicinal Chemistry, Organic Pharmacology & Pharmacy Chemistry Article MGLUR1 ANTAGONISTS RAT DISORDERS PROFILE PHARMACOLOGY KNOCKDOWN ALLODYNIA DISCOVERY PROSPECTS BRAIN mGluR1 antagonist Metabotropic glutamate receptor Neuropathic pain Schizophrenia Aryl isoxazole