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.
Jin
Haolun
H
Gilead Sciences, Inc. 333 Lakeside Drive, Foster City, CA 94404, USA. hjin@gilead.com
Cai
Ruby Z
RZ
Schacherer
Laura
L
Jabri
Salman
S
Tsiang
Manuel
M
Fardis
Maria
M
Chen
Xiaowu
X
Chen
James M
JM
Kim
Choung U
CU
D015195:Drug Design; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D009287:Naphthyridines / Q000737:chemistry; D013329:Structure-Activity Relationship
D019428:HIV Integrase Inhibitors; C489415:L870810; D009287:Naphthyridines