Oximinoarylsulfonamides as potent HIV protease inhibitors

The need for a potent HIV protease inhibitor (PI) to combat emerging PI-resistant viruses is anticipated. Analogs formulated from the combination of structural fragments of Ritonavir, Lopinavir, and Amprenavir were synthesized. Analogs containing the oxime pharmacophore were found to have improved activities against both wild type and resistant (A17) viruses. The synthesis and structure–activity relationships (SAR) based upon the in vitro IC50 of this series of compounds are reported.

Graphical abstractA novel series of arylsulfonamides with various R1 and R2 groups were prepared and evaluated as HIV protease inhibitors against both the wild type and A17 resistant viruses. The X-ray crystal structure of the most active oxime analog bound in the enzyme active site is presented.Figure optionsDownload full-size imageDownload as PowerPoint slide