Mechanism-based design of 2,3-benzodiazepine inhibitors for AMPA receptors.
10.1016/j.apsb.2015.07.007
- Author:
Li NIU
1
Author Information
1. Chemistry Department, University at Albany, State University of New York, Albany, NY 12222, USA.
- Publication Type:Journal Article
- Keywords:
2,3-Benzodiazepine derivatives;
AMPA receptors;
RNA aptamers;
Subunit-selective antagonists
- From:
Acta Pharmaceutica Sinica B
2015;5(6):500-505
- CountryChina
- Language:English
-
Abstract:
2,3-Benzodiazepine (2,3-BDZ) compounds represent a group of structurally diverse, small-molecule antagonists of (R, S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptors. Antagonists of AMPA receptors are drug candidates for potential treatment of a number of neurological disorders such as epilepsy, stroke and amyotrophic lateral sclerosis (ALS). How to make better inhibitors, such as 2,3-BDZs, has been an enduring quest in drug discovery. Among a few available tools to address this specific question for making better 2,3-BDZs, perhaps the best one is to use mechanistic clues from studies of the existing antagonists to design and discover more selective and more potent antagonists. Here I review recent work in this area, and propose some ideas in the continuing effort of developing newer 2,3-BDZs for tighter control of AMPA receptor activities in vivo.
