Design, synthesis, and SAR studies of novel and highly active tri-cyclic HIV integrase inhibitors

A novel class of tri-cyclic HIV integrase inhibitors were designed based on conformational analysis of 1,6-naphthyridine carboxamide compound L-870810 and docking the designed inhibitor into the active site of our integrase enzyme model. The efficient syntheses of pyrroloquinoline tri-cyclic analogs are described. The SAR studies resulted in the identification of a lead compound that is more potent and more soluble than L-870810.

A novel class of tri-cyclic HIV integrase inhibitors were designed based on the conformational analysis of inhibitors for binding. SAR studies led to the identification of compound 1 exhibiting potent anti-HIV activity with EC50 = 3.4 nM and favorable physicochemical properties.Figure optionsDownload as PowerPoint slide