Synthesis and biological evaluation of aryl isoxazole derivatives as metabotropic glutamate receptor 1 antagonists

A potential treatment for neuropathic pain

Gyeong Hi Cho, Taehun Kim, Woo Seung Son, Seon Hee Seo, Sun Joon Min, Yong Seo Cho, Gyochang Keum, Kyu-Sung Jeong, Hun Yeong Koh, Jiyoun Lee, Ae Nim Pae

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1324-1328
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume25
Issue number6
DOIs
Publication statusPublished - 2015 Mar 15

Fingerprint

Isoxazoles
Excitatory Amino Acid Antagonists
Neuralgia
Derivatives
Brain
Ionotropic Glutamate Receptors
Therapeutics
Metabotropic Glutamate Receptors
Glutamate Receptors
Brain Diseases
Scaffolds
Chronic Pain
Neurotransmitter Agents
Glutamic Acid
Schizophrenia
Animals
Anxiety
Animal Models
metabotropic glutamate receptor type 1
Pain

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

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. / Synthesis and biological evaluation of aryl isoxazole derivatives as metabotropic glutamate receptor 1 antagonists : A potential treatment for neuropathic pain. In: Bioorganic and Medicinal Chemistry Letters. 2015 ; Vol. 25, No. 6. pp. 1324-1328.
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Synthesis and biological evaluation of aryl isoxazole derivatives as metabotropic glutamate receptor 1 antagonists : A potential treatment for neuropathic pain. / 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.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 25, No. 6, 15.03.2015, p. 1324-1328.

Research output: Contribution to journalArticle

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AU - Pae, Ae Nim

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