Discovery, synthesis, and structure-activity relationships of 2-aminoquinazoline derivatives as a novel class of metabotropic glutamate receptor 5 negative allosteric modulators

Autor:	Holger Kubas, Ilya Pyatkin, Maksims Vanejevs, Ulrich Abel, Udo Meyer, Mirko Hechenberger, Valerjans Kauss, Raisa Ambartsumova, Alexey I. Polosukhin, Bjoern Krueger, Ronalds Zemribo
Rok vydání:	2013
Předmět:	Models Molecular Allosteric modulator Toluidines Stereochemistry Receptor Metabotropic Glutamate 5 Clinical Biochemistry Allosteric regulation Drug Evaluation Preclinical Pharmaceutical Science Receptors Metabotropic Glutamate Biochemistry Inhibitory Concentration 50 Structure-Activity Relationship User-Computer Interface Allosteric Regulation Drug Discovery Animals Humans Molecular Biology Cells Cultured Quinazolinones Virtual screening Chemistry Metabotropic glutamate receptor 5 Organic Chemistry Rational design Rats Metabotropic glutamate receptor Quinazolines Molecular Medicine Metabotropic glutamate receptor 1 Metabotropic glutamate receptor 2
Zdroj:	Bioorganicmedicinal chemistry letters. 23(16)
ISSN:	1464-3405
Popis:	A virtual screening approach using various in silico methodologies led to the discovery of 2-(m-tolylamino)-7,8-dihydroquinazolin-5(6H)-one (1) as a moderately active negative allosteric modulator (NAM) of the metabotropic glutamate receptor subtype 5 (mGluR5) showing high selectivity against the subtype mGluR1. Modifications of the parent compound by rational design yielded a series of highly potent derivatives which will serve as valuable starting points for further hit-to-lead optimization efforts toward a suitable drug candidate for the treatment of L-DOPA induced dyskinesia.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4568815830ffcb642bbde0d72aa43186 https://pubmed.ncbi.nlm.nih.gov/23856046 Zobrazit plný text záznamu Full Text from ScienceDirect