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.
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. jim_guare@merck.com
James P
JP
Guare
John S
JS
Wai
Robert P
RP
Gomez
Neville J
NJ
Anthony
Samson M
SM
Jolly
Amanda R
AR
Cortes
Joseph P
JP
Vacca
Peter J
PJ
Felock
Kara A
KA
Stillmock
William A
WA
Schleif
Gregory
G
Moyer
Lori J
LJ
Gabryelski
Lixia
L
Jin
I-Wu
IW
Chen
Daria J
DJ
Hazuda
Steven D
SD
Young
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