Discovery of dimeric inhibitors by extension into the entrance channel of HIV-1 reverse transcriptase

Design of non-nucleoside inhibitors of HIV-1 reverse transcriptase is being pursued with computational guidance. Extension of azine-containing inhibitors into the entrance channel between Lys103 and Glu138 has led to the discovery of potent and structurally novel derivatives including dimeric inhibitors in an NNRTI-linker-NNRTI motif.

Graphical abstractDesign of non-nucleoside inhibitors of HIV-1 reverse transcriptase is being pursued with computational guidance. Extension of azine-containing inhibitors into the entrance channel between Lys103 and Glu138 has led to the discovery of potent and structurally novel derivatives including dimeric inhibitors in an NNRTI-linker-NNRTI motif.Figure optionsDownload full-size imageDownload as PowerPoint slide