Novel thienopyrimidinones as mGluR1 antagonists

Title
Novel thienopyrimidinones as mGluR1 antagonists
Authors
김영재김지연김소라기유란서선희태진성고민경장현서임은정송치만조윤정고혜영정유훈추일한금교창민선준추현아
Keywords
mGluR1 antagonist; thienopyrimidinone; CNS disease; glutamate; metabotropic
Issue Date
2014-10
Publisher
European journal of medicinal chemistry
Citation
VOL 85, 629-637
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.
URI
http://pubs.kist.re.kr/handle/201004/48016
ISSN
02235234
Appears in Collections:
KIST Publication > Article
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