title: Synthesis and biological evaluation of aryl isoxazole derivatives as metabotropic glutamate receptor 1 antagonists: a potential treatment for neuropathic pain.
abstract: 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.
authors: Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea; Department of Chemistry, Yonsei University, Seodaemun-gu, Seoul 120-749, Republic of Korea.
authors: Gyeong Hi
authors: GH
authors: Cho
authors: Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea; Biological Chemistry, Korea University of Science and Technology, Yuseong-Gu, Daejon 305-350, Republic of Korea.
authors: TaeHun
authors: T
authors: Kim
authors: Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea; Department of Chemistry, Yonsei University, Seodaemun-gu, Seoul 120-749, Republic of Korea.
authors: Woo Seung
authors: WS
authors: Son
authors: Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
authors: Seon Hee
authors: SH
authors: Seo
authors: Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
authors: Sun-Joon
authors: SJ
authors: Min
authors: Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
authors: Yong Seo
authors: YS
authors: Cho
authors: Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
authors: Gyochang
authors: G
authors: Keum
authors: Department of Chemistry, Yonsei University, Seodaemun-gu, Seoul 120-749, Republic of Korea.
authors: Kyu-Sung
authors: KS
authors: Jeong
authors: Department of Chemistry, Inha University, Nam-gu, Incheon 402-751, Republic of Korea.
authors: Hun Yeong
authors: HY
authors: Koh
authors: Department of Global Medical Science, Sungshin University, Seoul 142-732, Republic of Korea. Electronic address: jlee@sungshin.ac.kr.
authors: Jiyoun
authors: J
authors: Lee
authors: Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea; Biological Chemistry, Korea University of Science and Technology, Yuseong-Gu, Daejon 305-350, Republic of Korea. Electronic address: anpae@kist.re.kr.
authors: Ae Nim
authors: AN
authors: Pae
mesh_terms: D000284:Administration, Oral; D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D007555:Isoxazoles / Q000737:chemistry* / Q000627:therapeutic use; D009437:Neuralgia / Q000139:chemically induced / Q000188:drug therapy*; D011485:Protein Binding; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D007555:Isoxazoles; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1
keywords: Aryl isoxazole; Metabotropic glutamate receptor; Neuropathic pain; Schizophrenia; mGluR1 antagonist