Difluoromethylbenzoxazole pyrimidine thioether derivatives : a novel class of potent non-nucleoside HIV-1 reverse transcriptase inhibitors - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Medicinal Chemistry Année : 2011

Difluoromethylbenzoxazole pyrimidine thioether derivatives : a novel class of potent non-nucleoside HIV-1 reverse transcriptase inhibitors

Résumé

This paper reports the synthesis and antiviral properties of new difluoromethylbenzoxazole (DFMB) pyrimidine thioether derivatives as non-nucleoside HIV-1 reverse transcriptase inhibitors. By use of a combination of structural biology study and traditional medicinal chemistry, several members of this novel class were synthesized using a single electron transfer chain process (radical nucleophilic substitution, S(RN)1) and were found to be potent against wild-type HIV-1 reverse transcriptase, with low cytotoxicity but with moderate activity against drug-resistant strains. The most promising compound 24 showed a significant EC(50) value close to 6.4 nM against HIV-1 IIIB, a moderate EC(50) value close to 54 μM against an NNRTI resistant double mutant (K103N + Y181C), but an excellent selectivity index >15477 (CC(50) > 100 μM).

Domaines

Chimie organique
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Dates et versions

hal-01162817 , version 1 (11-06-2015)

Identifiants

  • HAL Id : hal-01162817 , version 1

Citer

Jérémie Boyer, Eric Arnoult, Maurice Médebielle, Jérôme Guillemont, Johan Unge, et al.. Difluoromethylbenzoxazole pyrimidine thioether derivatives : a novel class of potent non-nucleoside HIV-1 reverse transcriptase inhibitors. Journal of Medicinal Chemistry, 2011, 54 (23), pp.7974-7985. ⟨hal-01162817⟩
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