Tricyclic HIV integrase inhibitors: VI. SAR studies of ‘benzyl flipped’ C3-substituted pyrroloquinolines

A series of C3 halobenzyl-substituted tricyclic HIV integrase inhibitors was prepared. Improvement in cell-based inhibitor potency was observed in comparison to previously disclosed tricyclic pyrroloquinolines carrying the ‘halobenzyl tail’ at the lactam nitrogen. Animal PK for several of the C3-substituted inhibitors was examined, with a dihaloaryl analog achieving good balance in protein-shifted EC50 and t1/2 in animal PK studies.

A series of C3-halobenzyl-substituted tricyclic integrase inhibitors was prepared. Excellent cell-based inhibitor potency was observed, and selected leads in this new series showed good bioavailability and long t1/2 in animal PK studies.Figure optionsDownload as PowerPoint slide