Novel substituted 2,3-benzodiazepin-4-ones as non-competitive AMPA antagonists and positive modulators

Abstract

Several substituted 2,3-benzodiazepin-4-ones are claimed as non-competitive AMPA antagonists and positive modulators of AMPA receptors. Some of these compounds are good to moderate AMPA receptor antagonists (IC₅₀ values = 0.8 - 26 μM) and positive allosteric modulators of the AMPA receptor. Some selected compounds showed good neuroprotection in the maximal electroshock assay (MES). Over 60 compounds are specifically claimed and synthetic methods for 54 compounds are presented. AMPA receptor antagonistic activity is reported for 9 compounds and the potentiation of the AMPA current has been reported for 7 compounds. These 2,3-benzodiazepines have been synthesised by several reported methodologies. These compounds will have utility in the treatment of various neurological and neurodegenerative diseases and disorders caused by over stimulation of excitatory amino acid receptors.

• AMPA
• 2,3-benzodiazepin-4-ones
• excitatory amino acid
• glutamate
• ischaemia
• neuroprotection
• non-competitive AMPA
• stroke