Eastern extension of azoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase; cyano group alternatives

Design of non-nucleoside inhibitors of HIV-1 reverse transcriptase is being pursued with the assistance of free energy perturbation (FEP) calculations to predict relative free energies of binding. Extension of azole-containing inhibitors into an ‘eastern’ channel between Phe227 and Pro236 has led to the discovery of potent and structurally novel derivatives.

Graphical abstractSynthesis, assaying, and computational results are reported for new anti-HIV agents that exhibit high potency and low cytotoxicity. Extension into an eastern channel in the HIV-1 reverse transcriptase binding site is investigated.Figure optionsDownload full-size imageDownload as PowerPoint slide