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

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

  • Bioorg Med Chem Lett. 2013 Aug 15;23(16):4493-500. doi: 10.1016/j.bmcl.2013.06.049.
Holger Kubas 1,  Udo Meyer,  Bjoern Krueger,  Mirko Hechenberger,  Maksims Vanejevs,  Ronalds Zemribo,  Valerjans Kauss,  Raisa Ambartsumova,  Ilya Pyatkin,  Alexey I Polosukhin,  Ulrich Abel
Affiliations

Affiliation

  • 1 Merz Pharmaceuticals GmbH, Eckenheimer Landstrasse 100, 60318 Frankfurt am Main, Germany.
PMID: 23856046 DOI: 10.1016/j.bmcl.2013.06.049
Abstract

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.

Keywords

Allosteric modulator; Metabotropic glutamate receptor; Virtual screening; l-DOPA induced dyskinesia; mGluR5.

Figures
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z