8-Methylureido-10-amino-10-methyl-imidazo[1,2-a]indeno[1,2-e] pyrazine-4-ones: Highly in vivo potent and selective AMPA receptor antagonists

Authors
Jimonet, P Cheve, M Bohme, GA Boireau, A Damour, D Debono, MW Genevois-Borella, A Imperato, A Pratt, J Randle, JCR Ribeill, Y Stutzmann, JM Vuilhorgne, M Mignani, S
Citation
P. Jimonet et al., 8-Methylureido-10-amino-10-methyl-imidazo[1,2-a]indeno[1,2-e] pyrazine-4-ones: Highly in vivo potent and selective AMPA receptor antagonists, BIO MED CH, 8(8), 2000, pp. 2211-2217
Citations number
23
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY
ISSN journal
09680896 → ACNP
Volume
8
Issue
8
Year of publication
2000
Pages
2211 - 2217
Database
ISI
SICI code
0968-0896(200008)8:8<2211:8P>2.0.ZU;2-G
Abstract
Water soluble 8-methylureido-10-amino-10-methyl-imidazo[1,2-a]indeno[1,2-e] pyrazine-4-one 4 represents a novel class of highly potent and selective AM PA receptors antagonists with in vivo activity. The dextrorotatory isomer ( +)-4 was found to display the highest affinity with an IC50 of 10 nM. It al so exhibited very good anticonvulsant effects after ip, sc and iv administr ation in mice subjected to electrical convulsions (MES) and ip in audiogeni c seizure-e in DBA/2 mice (ED50's less than or equal to 10 mg/kg). (C) 2000 Elsevier Science Ltd. All rights reserved.