title: Design, synthesis, and SAR studies of novel and highly active tri-cyclic HIV integrase inhibitors.
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.
authors.affiliation: Gilead Sciences, Inc. 333 Lakeside Drive, Foster City, CA 94404, USA. hjin@gilead.com
authors.forename: Haolun
authors.initials: H
authors.lastname: Jin
authors.forename: Ruby Z
authors.initials: RZ
authors.lastname: Cai
authors.forename: Laura
authors.initials: L
authors.lastname: Schacherer
authors.forename: Salman
authors.initials: S
authors.lastname: Jabri
authors.forename: Manuel
authors.initials: M
authors.lastname: Tsiang
authors.forename: Maria
authors.initials: M
authors.lastname: Fardis
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Chen
authors.forename: James M
authors.initials: JM
authors.lastname: Chen
authors.forename: Choung U
authors.initials: CU
authors.lastname: Kim
mesh_terms: D015195:Drug Design; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D009287:Naphthyridines / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D019428:HIV Integrase Inhibitors; C489415:L870810; D009287:Naphthyridines