4,10-dihydro-4-oxo-4H-imidazo[1,2-a]indeno[1,2-e]pyrazin-2-carboxylic acidderivatives: Highly potent and selective AMPA receptors antagonists with in vivo activity

A novel series of 2-substituted-4,5-dihydro-4-oxo-4H-imidazo[1,2-a]indeno[1 ,2-e]pyrazine derivatives was synthesised. One of them, 4e-a highly water s oluble compound - exhibited a nanomolar affinity and demonstrated competiti ve antagonist properties at the ionotropic AMPA receptors. This compound al so displayed potent anticonvulsant properties against electrically or sound -induced convulsions in mice after systemic administration, thus suggesting adequate brain penetration. (C) 2000 Elsevier Science Ltd. All rights rese rved.