A series of 5-aminosubstituted 4-fluorobenzyl-8-hydroxy-[1,6]naphthyridine-7-carboxamide HIV-1 integrase inhibitors

被引：41

作者：

Guare, JP ^{[1
]}

Wai, JS

Gomez, RP

Anthony, NJ

Jolly, SM

Cortes, AR

Vacca, JP

Felock, PJ

Stillmock, KA

Schleif, WA

Moyer, G

Gabryelski, LJ

Jin, LX

Chen, IW

Hazuda, DJ

Young, SD

机构：

[1] Merck Res Labs, Dept Med Chem, West Point, PA 19486 USA

[2] Merck Res Labs, Dept Biol Chem, West Point, PA 19486 USA

[3] Merck Res Labs, Dept Vaccine & Biol Res, West Point, PA 19486 USA

[4] Merck Res Labs, Dept Drug Metab & Pharmacol, West Point, PA 19486 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 11期

关键词：

HIV-1; integrase; inhibitor; monkey; rhesus; macaque; naphthyridine;

D O I：

10.1016/j.bmcl.2006.03.003

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：2900 / 2904

页数：5

共 14 条

[1]

Anthony N. J., 2002, [No title captured], Patent No. [WO0230930, 0230930]

[2] HIV-1 integrase: A target for new AIDS chemotherapeutics [J].

Anthony, NJ .

CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2004, 4 (09) :979-990

[3] Surveying for surfaces that resist the adsorption of proteins [J].

Chapman, RG ;

Ostuni, E ;

Takayama, S ;

Holmlin, RE ;

Yan, L ;

Whitesides, GM .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2000, 122 (34) :8303-8304

[4] Structure and function of HIV-1 integrase [J].

Chiu, TK ;

Davies, DR .

CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2004, 4 (09) :965-977

[5] A series of 5-(5,6)-dihydrouracil substituted 8-hydroxy-[1,6]naphthyridine-7-carboxylic acid 4-fluorobenzylamide inhibitors of HIV-1 integrase and viral replication in cells [J].

Embrey, MW ;

Wai, JS ;

Funk, TW ;

Homnick, CF ;

Perlow, DS ;

Young, SD ;

Vacca, JP ;

Hazuda, DJ ;

Felock, PJ ;

Stillmock, KA ;

Witmer, MV ;

Moyer, G ;

Schleif, WA ;

Gabryelski, LJ ;

Jin, LX ;

Chen, IW ;

Ellis, JD ;

Wong, BK ;

Lin, JH ;

Leonard, YM ;

Tsou, NN ;

Zhuang, LH .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (20) :4550-4554

[6] Structure of the HIV-1 integrase catalytic domain complexed with an inhibitor: A platform for antiviral drug design [J].

Goldgur, Y ;

Craigie, R ;

Cohen, GH ;

Fujiwara, T ;

Yoshinaga, T ;

Fujishita, T ;

Sugimoto, H ;

Endo, T ;

Murai, H ;

Davies, DR .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (23) :13040-13043

[7] Differential divalent cation requirements uncouple the assembly and catalytic reactions of human immunodeficiency virus type 1 integrase [J].

Hazuda, DJ ;

Felock, PJ ;

Hastings, JC ;

Pramanik, B ;

Wolfe, AL .

JOURNAL OF VIROLOGY, 1997, 71 (09) :7005-7011

[8] A naphthyridine carboxamide provides evidence for discordant resistance between mechanistically identical inhibitors of HIV-1 integrase [J].

Hazuda, DJ ;

Anthony, NJ ;

Gomez, RP ;

Jolly, SM ;

Wai, JS ;

Zhuang, LH ;

Fisher, TE ;

Embrey, M ;

Guare, JP ;

Egbertson, MS ;

Vacca, JP ;

Huff, JR ;

Felock, PJ ;

Witmer, MV ;

Stillmock, KA ;

Danovich, R ;

Grobler, J ;

Miller, MD ;

Espeseth, AS ;

Jin, LX ;

Chen, IW ;

Lin, JH ;

Kassahun, K ;

Ellis, JD ;

Wong, BK ;

Xu, W ;

Pearson, PG ;

Schleif, WA ;

Cortese, R ;

Emini, E ;

Summa, V ;

Holloway, MK ;

Young, SD .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (31) :11233-11238

[9] Integrase inhibitors and cellular immunity suppress retroviral replication in rhesus macaques [J].

Hazuda, DJ ;

Young, SD ;

Guare, JP ;

Anthony, NJ ;

Gomez, RP ;

Wai, JS ;

Vacca, JP ;

Handt, L ;

Motzel, SL ;

Klein, HJ ;

Dornadula, G ;

Danovich, RM ;

Witmer, MV ;

Wilson, KAA ;

Tussey, L ;

Schleif, WA ;

Gabryelski, LS ;

Jin, LX ;

Miller, MD ;

Casimiro, DR ;

Emini, EA ;

Shiver, JW .

SCIENCE, 2004, 305 (5683) :528-532

[10] RAPID NAD+-LINKED ASSAY FOR MICROSOMAL URIDINE-DIPHOSPHATE GLUCURONYLTRANSFERASE OF RAT-LIVER AND SOME OBSERVATIONS ON SUBSTRATE-SPECIFICITY OF ENZYME [J].

MULDER, GJ ;

VANDOORN, ABD .

BIOCHEMICAL JOURNAL, 1975, 151 (01) :131-140

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