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, Mina; Kim, TaeHun; Kwak, Jinsook; Seo, Seon Hee; Ko, Min Kyung; Lim, Eun Jeong; Min, Sun-Joon; Cho, Yong Seo; Keum, Gyochang; Baek, Du-Jong; Lee, Jiyoun; Pae, 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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