Referenced in: none

Automatically associated channels: Kv11.1

Title: Novel thienopyrimidinones as mGluR1 antagonists.

Authors: Youngjae Kim, Jeeyeon Kim, Sora Kim, Yooran Ki, Seon Hee Seo, Jinsung Tae, Min Kyung Ko, Hyun-Seo Jang, Eun Jeong Lim, Chiman Song, YoonJeong Cho, Hae-Young Koh, Youhoon Chong, Il Han Choo, Gyochang Keum, Sun-Joon Min, Hyunah Choo

Journal, date & volume: Eur J Med Chem, 2014 Oct 6 , 85, 629-37

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25127154

Abstract
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 μM), 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.