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

  • Bioorg Med Chem Lett. 2006 Aug 1;16(15):3989-92. doi: 10.1016/j.bmcl.2006.05.016.
Haolun Jin  1 ,  Ruby Z Cai ,  Laura Schacherer ,  Salman Jabri ,  Manuel Tsiang ,  Maria Fardis ,  Xiaowu Chen ,  James M Chen ,  Choung U Kim
Affiliations
  • 1. Gilead Sciences, Inc. 333 Lakeside Drive, Foster City, CA 94404, USA. [email protected]
PMID: 16723225 DOI: 10.1016/j.bmcl.2006.05.016
Abstract

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.