Related Experiment Video
Updated: May 28, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Difluoromethylbenzoxazole pyrimidine thioether derivatives: a novel class of potent non-nucleoside HIV-1 reverse
Jérémie Boyer1, Eric Arnoult, Maurice Médebielle
1Université de Lyon, Université Claude Bernard Lyon 1, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, UMR CNRS-UCBL-INSA, Equipe Synthèse de Molécules d'Intérêt Thérapeutique, Bâtiment Curien, 43 Boulevard du 11 Novembre 1918, F-69622 Villeurbanne, France.
Abstract:
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).
Related Concept Videos
Antiviral Nucleoside Inhibitors
Inhibitors of Viral Protein Synthesis
Inhibitors of Bacterial DNA Synthesis
Inhibitors Of Virion Release
Inhibitors of Virion Maturation and Assembly
Electrophilic Aromatic Substitution: Fluorination and Iodination of Benzene

