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8-Methylureido-4,5-dihydro-4-oxo-10H-imidazo[1,2-a]indeno[1,2-e]pyrazines: highly potent in vivo AMPA antagonists.

Abstract：

:A novel series of readily water soluble 8-methylureido-4,5-dihydro-4-oxo-10H-imidazo[1,2-a]indeno[1,2-e]++ +pyrazines were synthesized. The -10-yl acetic acid ((+)-3) and -10-carboxylidene (4) derivatives exhibit potent affinities (IC50=4 and 19 nM, respectively) and antagonist properties (IC50 = 2 and 3 nM, respectively) at the ionotropic AMPA receptor. These compounds also display anticonvulsant properties against both electrically and sound-induced convulsions in mice after ip, sc and iv administration with ED50 values between 0.9 and 11 mg/kg, thus suggesting adequate brain penetration.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Mignani S,Bohme GA,Boireau A,Cheve M,Damour D,Debono MW,Genevois-Borella A,Imperato A,Jimonet P,Pratt J,Randle JC,Ribeill Y,Vuilhorgne M,Stutzmann JM

doi

10.1016/s0960-894x(00)00054-8

subject

Has Abstract

pub_date

2000-03-20 00:00:00

pages

591-6

issue

6

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(00)00054-8

journal_volume

10

pub_type

杂志文章

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