Synthesis and biological evaluation of picolinamides and thiazole-2-carboxamides as mGluR5 (metabotropic glutamate receptor 5) antagonists

Hoang Nam Vu, Ji Young Kim, Ahmed H E Hassan, Kihang Choi, Jong Hyun Park, Ki Duk Park, Jae Kyun Lee, Ae Nim Pae, Hyunah Choo, Sun Joon Min, Yong Seo Cho

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

We described here the synthesis and biological evaluation of picolinamides and thiazole-2-carboxamides as potential mGluR5 antagonists. We found that a series of thiazole derivatives 6 showed better inhibitory activity against mGluR5. Compounds 6bc and 6bj have been identified as potent antagonists (IC50 = 274 and 159 nM) showing excellent in vitro stability profile. Molecular docking study using the crystal structure of mGluR5 revealed that our compounds 6bc and 6bj fit the allosteric binding site of mavoglurant well.

Original languageEnglish
Pages (from-to)140-144
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume26
Issue number1
DOIs
Publication statusPublished - 2016 Jan 1

Fingerprint

Metabotropic Glutamate 5 Receptor
Thiazoles
Excitatory Amino Acid Antagonists
Metabotropic Glutamate Receptors
Allosteric Site
Inhibitory Concentration 50
Binding Sites
Crystal structure
Derivatives
picolinamide

Keywords

  • Antagonist
  • Metabotropic glutamate receptor
  • Molecular docking
  • Picolinamides
  • Thiazole-2-carboxamides

ASJC Scopus subject areas

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

Cite this

Synthesis and biological evaluation of picolinamides and thiazole-2-carboxamides as mGluR5 (metabotropic glutamate receptor 5) antagonists. / Vu, Hoang Nam; Kim, Ji Young; Hassan, Ahmed H E; Choi, Kihang; Park, Jong Hyun; Park, Ki Duk; Lee, Jae Kyun; Pae, Ae Nim; Choo, Hyunah; Min, Sun Joon; Cho, Yong Seo.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 26, No. 1, 01.01.2016, p. 140-144.

Research output: Contribution to journalArticle

Vu, Hoang Nam ; Kim, Ji Young ; Hassan, Ahmed H E ; Choi, Kihang ; Park, Jong Hyun ; Park, Ki Duk ; Lee, Jae Kyun ; Pae, Ae Nim ; Choo, Hyunah ; Min, Sun Joon ; Cho, Yong Seo. / Synthesis and biological evaluation of picolinamides and thiazole-2-carboxamides as mGluR5 (metabotropic glutamate receptor 5) antagonists. In: Bioorganic and Medicinal Chemistry Letters. 2016 ; Vol. 26, No. 1. pp. 140-144.
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AU - Choi, Kihang

AU - Park, Jong Hyun

AU - Park, Ki Duk

AU - Lee, Jae Kyun

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