Discovery and biological evaluation of tetrahydrothieno[2,3-c]pyridine derivatives as selective metabotropic glutamate receptor 1 antagonists for the potential treatment of neuropathic pain

Authors
Nam, MinaKim, TaeHunKwak, JinsookSeo, Seon HeeKo, Min KyungLim, Eun JeongMin, Sun-JoonCho, Yong SeoKeum, GyochangBaek, Du-JongLee, JiyounPae, Ae Nim
Issue Date
2015-06-05
Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
Citation
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v.97, pp.245 - 258
Abstract
Metabotropic glutamate receptor 1 (mGluR1) has been a prime target for drug discovery due to its heavy involvement in various brain disorders. Recent studies suggested that mGluR1 is associated with chronic pain and can serve as a promising target for the treatment of neuropathic pain. In an effort to develop a novel mGluR1 antagonist, we designed and synthesized a library of compounds with tetrahydrothieno [2,3-c]pyridine scaffold. Among these compounds, compound 9b and 10b showed excellent antagonistic activity in vitro and demonstrated pain-suppressing activity in animal models of pain. Both compounds were orally active, and compound 9b exhibited a favorable pharmacokinetic profile in rats. We believe that these compounds can provide a promising lead compound that is suitable for the potential treatment of neuropathic pain. (C) 2015 Elsevier Masson SAS. All rights reserved.
Keywords
LONG-TERM DEPRESSION; ALLOSTERIC MODULATORS; MGLUR1 ANTAGONISTS; DRUG DISCOVERY; BRAIN; RAT; PHARMACOLOGY; KNOCKDOWN; ALLODYNIA; INDUCTION; LONG-TERM DEPRESSION; ALLOSTERIC MODULATORS; MGLUR1 ANTAGONISTS; DRUG DISCOVERY; BRAIN; RAT; PHARMACOLOGY; KNOCKDOWN; ALLODYNIA; INDUCTION; mGluR1 antagonist; Metabotropic glutamate receptor; Neuropathic pain; Thiophene derivatives
ISSN
0223-5234
URI
https://pubs.kist.re.kr/handle/201004/125335
DOI
10.1016/j.ejmech.2015.04.060
Appears in Collections:
KIST Article > 2015
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