Kim, Youngjae Kim, Jeeyeon Kim, Sora Ki, Yooran Seo, Seon Hee Tae, Jinsung Ko, Min Kyung Jang, Hyun-Seo Lim, Eun Jeong Song, Chiman Cho, YoonJeong Koh, Hae-Young Chong, Youhoon Choo, Il Han Keum, Gyochang Min, Sun-Joon Choo, Hyunah 2024-01-20T08:34:12Z 2024-01-20T08:34:12Z 2021-09-02 2014-10-06 0223-5234 https://pubs.kist.re.kr/handle/201004/126252 There has been much attention to discover mGluR1 antagonists for treating various central nervous system diseases such as seizures and neuropathic pain. Thienopyrimidinone derivatives were designed, synthesized, and biologically evaluated against mGluR1. Among the synthesized compounds, 3-(4-methoxyphenyl)-7-(o-tolyl)thienopyrimidin-4-one 30 exhibited the most potent inhibitory activity with an IC50 value of 45 nM and good selectivity over mGluR5. Also, the selective mGluR1 antagonist 30 showed marginal hERG channel activity (IC50 = 9.87 mu M), good profiles to CYP isozymes, and a good pharmacokinetic profile. Overall, the compound 30 was identified as a selective mGluR1 antagonist with a good pharmacokinetic profile, which is probably devoid of cardiac side effect and drug drug interactions. Therefore, the compound 30 can be expected to be broadly used as mGluR1 antagonistic chemical probe in in vitro and in vivo study for investigating CNS diseases. (C) 2014 Elsevier Masson SAS. All rights reserved. English ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER METABOTROPIC GLUTAMATE-RECEPTOR NEUROPATHIC PAIN DRUG DISCOVERY IN-VITRO DERIVATIVES INHIBITION EXPRESSION CHANNELS PYRROLES SUBTYPES Novel thienopyrimidinones as mGluR1 antagonists Article 10.1016/j.ejmech.2014.08.027 1 EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v.85, pp.629 - 637 EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 85 629 637 scie scopus 000342859700053 Chemistry, Medicinal Pharmacology & Pharmacy Article METABOTROPIC GLUTAMATE-RECEPTOR NEUROPATHIC PAIN DRUG DISCOVERY IN-VITRO DERIVATIVES INHIBITION EXPRESSION CHANNELS PYRROLES SUBTYPES mGluR1 antagonist Thienopyrimidinone CNS disease Glutamate Metabotropic