Michel Cheve

Chirality directed self-assembly. Resolution of 2,5-diazabicyclo[2.2.2]octane-3,6-dione and crystal structures of its racemic and (−) enantiomeric forms

The chiral bicyclic bis-lactam 1 has been resolved and the crystal structures of the racemate (±)-1 and of enantiomerically pure (−)-1 have been determined. They show that the chiral nature of the substance determines the supramolecular architecture generated by hydrogen bonding self-assembly, giving an infinite zig-zag chain for the racemate and a cyclic tetramer for the enantiomer.

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

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.

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

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.

Optical isomers of RP 64406: New potent antiglutamate agents

Abstract Optical isomers of the riluzole derivative, sulfoxide RP 64406, were prepared in pure forms. No significant difference was found between the (+) and (−) isomers in their powerful antiglutamate activity.

From Random Screening of Chemical Libraries to the Optimization of FPP-Competitive Inhibitors of Farnesyltransferase

Together with gene alterations of the p53 tumor suppressor gene, mutations of the ras genes represent the most frequent gene modification umancancers. Ras mutations are found in at least 90% of pancreas, 50% of colon, and 30% of both lung and thyroid cancers (1,2).