摘要
2,3-Benzodiazepine(2,3-BDZ) compounds represent a group of structurally diverse,smallmolecule 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.
2,3-Benzodiazepine(2,3-BDZ) compounds represent a group of structurally diverse,smallmolecule 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.
基金
supported by NIH/NINDS Grant R01 NS060812
a grant from Muscular Dystrophy Association(MDA)
