Spiro-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one derivatives are mixed AMPA and NMDA glycine-site antagonists active in vivo

P Jimonet; A Boireau; M Chevé; D Damour; A Genevois-Borella; A Imperato; J Pratt; J C Randle; Y Ribeill; J M Stutzmann; S Mignani

doi:10.1016/s0960-894x(99)00502-8

Spiro-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one derivatives are mixed AMPA and NMDA glycine-site antagonists active in vivo

Bioorg Med Chem Lett. 1999 Oct 18;9(20):2921-6. doi: 10.1016/s0960-894x(99)00502-8.

Authors

P Jimonet¹, A Boireau, M Chevé, D Damour, A Genevois-Borella, A Imperato, J Pratt, J C Randle, Y Ribeill, J M Stutzmann, S Mignani

Affiliation

¹ Rhône-Poulenc S.A., Rhône-Poulenc Rorer, Centre de Recherche de Vitry-Alfortville, Vitry-sur-Seine, France.

PMID: 10571148
DOI: 10.1016/s0960-894x(99)00502-8

Abstract

Original spiro-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one derivatives were synthesised and led to the identification of 3e which showed good affinities for both the AMPA and the NMDA glycine-site receptors, and displayed good anticonvulsant effects after i.p. and i.v. administrations in the electroshock-induced convulsion assay in mice. The corresponding dextrorotatory isomer (+)-3e was notably more potent than the levorotatory isomer (-)-3e in in vitro and in vivo assays.

MeSH terms

Animals
Binding Sites
Excitatory Amino Acid Antagonists / chemistry
Excitatory Amino Acid Antagonists / metabolism
Excitatory Amino Acid Antagonists / pharmacology*
Glycine / metabolism*
Mice
Pyrazines / chemistry
Pyrazines / metabolism
Pyrazines / pharmacology*
Receptors, AMPA / antagonists & inhibitors*
Receptors, AMPA / metabolism
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
Receptors, N-Methyl-D-Aspartate / metabolism
Spiro Compounds / chemistry
Spiro Compounds / metabolism
Spiro Compounds / pharmacology*
Structure-Activity Relationship

Substances

Excitatory Amino Acid Antagonists
Pyrazines
Receptors, AMPA
Receptors, N-Methyl-D-Aspartate
Spiro Compounds
Glycine