4,10-Dihydro-4-oxo-4H-imidazo[1,2-a]indeno[1,2-e]pyrazin-2-carboxylic acid derivatives: highly potent and selective AMPA receptors antagonists with in vivo activity

  • Bioorg Med Chem Lett. 2000 May 15;10(10):1133-7. doi: 10.1016/s0960-894x(00)00181-5.
J M Stutzmann  1 ,  G A Bohme ,  A Boireau ,  D Damour ,  M W Debono ,  A Genevois-Borella ,  A Imperato ,  P Jimonet ,  J Pratt ,  J C Randle ,  Y Ribeill ,  M Vuilhorgne ,  S Mignani
Affiliations
  • 1. Aventis Pharma S.A., Centre de Recherche de Vitry-Alfortville, Vitry-sur-Seine, France.
PMID: 10843235 DOI: 10.1016/s0960-894x(00)00181-5
Abstract

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 soluble compound exhibited a nanomolar affinity and demonstrated competitive antagonist properties at the ionotropic AMPA receptors. This compound also displayed potent anticonvulsant properties against electrically or sound-induced convulsions in mice after systemic administration, thus suggesting adequate brain penetration.