A series of 5-aminosubstituted 4-fluorobenzyl-8-hydroxy-[1,6]naphthyridine-7-carboxamide HIV-1 integrase inhibitors.
A series of 5-amino derivatives of 8-hydroxy[1,6]-naphthyridine-7-carboxamide exhibiting sub-micromolar potency against replication of HIV-1 in cell culture was identified. One of these analogs, compound 12, displayed excellent pharmacokinetic properties when dosed orally in rats and in monkeys. This compound was demonstrated to be efficacious against replication of simian-human immunodeficiency virus (SHIV) 89.6P in infected rhesus macaques.
Guare
James P
JP
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. jim_guare@merck.com
Wai
John S
JS
Gomez
Robert P
RP
Anthony
Neville J
NJ
Jolly
Samson M
SM
Cortes
Amanda R
AR
Vacca
Joseph P
JP
Felock
Peter J
PJ
Stillmock
Kara A
KA
Schleif
William A
WA
Moyer
Gregory
G
Gabryelski
Lori J
LJ
Jin
Lixia
L
Chen
I-Wu
IW
Hazuda
Daria J
DJ
Young
Steven D
SD
D000586:Amination; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009287:Naphthyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D019428:HIV Integrase Inhibitors; D009287:Naphthyridines