par Le Van, Kiet 
;Cauvin, Christine;De Walque, Stéphane ;Georges, Benoît;Boland, Sandro;Martinelli, Valérie ;Demonte, Dominique ;Durant, François;Hevesi, László;Van Lint, Carine
Référence Journal of medicinal chemistry, 52, 12, page (3636-3643)
Publication Publié, 2009
;Cauvin, Christine;De Walque, Stéphane ;Georges, Benoît;Boland, Sandro;Martinelli, Valérie ;Demonte, Dominique ;Durant, François;Hevesi, László;Van Lint, Carine Référence Journal of medicinal chemistry, 52, 12, page (3636-3643)
Publication Publié, 2009
Article révisé par les pairs
| Résumé : | Several 5-ethyl-6-methyl-4-cycloalkyloxy-pyridin-2(1H)-ones were synthesized and evaluated for their anti HIV-1 activities against wild-type virus and clinically relevant mutant strains. A racemic mixture (10) with methyl substituents at positions 3 and 5 of the cyclohexyloxy moiety had potent antiviral activity against wild-type HIV-1. Subsequent stereoselective synthesis of a stereoisomer displaying both methyl groups in equatorial position was found to have the best EC(50). Further modulations focused on position 3 of the pyridinone ring improved the antiviral activity against mutant viral strains. Compounds bearing a 3-ethyl (22) or 3-isopropyl group (23) had the highest activity against wild-type HIV-1 and displayed low-nanomolar potency against several clinically relevant mutant strains. |
