Mechanism-based design of 2,3-benzodiazepine inhibitors for AMPA receptors

• Main Author: Li Niu
• Format: Article
• Language: English
• Published: Elsevier 2015-11-01
• Series: Acta Pharmaceutica Sinica B
• Subjects: AMPA receptors; 2,3-Benzodiazepine derivatives; Subunit-selective antagonists; RNA aptamers
• Online Access: http://www.sciencedirect.com/science/article/pii/S221138351500115X

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.