Jean-Francois Peyronel

Synthesis of RPR 100893, prototype of a new series of potent and selective non peptide NK1 antagonists : the triarylperhydroisoindolols.

Abstract The synthesis of enentiomerically pure RPR 100893, a novel non peptide NK1 Substance P antagonist, is described. This compound is a representative of 7,7,4-triaryl perhydroisoindol-4-ols, a new series of perhydroisoindole Substance P antagonists with high affinity for human NK 1 receptor.

Synthesis of RP-67,580, a new potent nonpeptide substance P antagonist

Abstract The synthesis of enantiomerically pure RP-67,580, a novel nonpeptide Substance P receptor antagonist, is described as well as the resolution of intermediate perhydroisoindolone.

1,3-Cycloaddition of chiral azomethine ylides generated from 2-(tert-butyl)-3-methylimidazolidin-4-one.

Abstract Chiral azomethine ylides, easily generated from 2-(tert-butyl)-3-methylimidazolidin-4-one and aldehydes, undergo 1,3-dipolar cycloadditions to activated alkenes. These reactions proceed with complete facial stereoselection. In the case of benzaldehyde and hexanal, the configurations of the 1,3-dipoles are also controlled and these ylides display high diastereoselectivity in their reactions with N-phenylmaleimide.

Synthesis of perhydrocyclopenta[c]pyrroles by a tandem rearrangement-autoxidation reaction

Abstract The reaction of the 5-mesylate derivative 7 in basic medium respectively gives in the absence of air, 2-t-butyloxycarbonyl-4,4-diphenyl-6-(2-methoxy-benzoyl) perhydrocyclopenta[c]pyrrole and in the presence of air, 2-t-butyloxycarbonyl-6,6-diphenyl-perhydrocyclopenta[c]pyrrol-4-one. The treatment of 2-t-butyloxycarbonyl-4,4-diphenyl-6-(2-methoxy-benzoyl) perhydrocyclopenta[c]pyrrole in basic medium with air affords 2-t-butyloxycarbonyl-6,6-diphenyl-perhydrocyclopenta[c]pyrrol-4-one. A mechanism is presented.

NEW DERIVATIVES OF 4,4-DIPHENYL-2-CYCLOHEXEN-ONE

Abstract The syntheses of some new derivatives of 4, 4-diphenyl-2-cyclohexen-one are reported. In particular, we described a palladium-based strategy for the preparation of dienes (1) and (2).

4,4-Diphenyl-7-perhydrothiapyrano[3,4-c]pyrrolone, a new series of substance P receptors antagonists

Abstract The synthesis of 4,4-Diphenyl-7-perhydrothiapyrano[3,4-c]pyrrolones, a new series of substance P antagonists with high affinity for rat and human NK1 receptors is described.

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).