Design and synthesis of novel β-diketo derivatives as HIV-1 integrase inhibitors

被引：35

作者：

Hu, Liming ^{[1
]}

Zhang, Sulei ^{[1
]}

He, Xianzhuo ^{[1
]}

Luo, Zaigang ^{[1
]}

Wang, Xiaoli ^{[1
]}

Liu, Wei ^{[1
]}

Qin, Xuemei ^{[1
]}

机构：

[1] Beijing Univ Technol, Coll Life Sci & Bioengn, Beijing 100124, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2012年 / 20卷 / 01期

基金：

北京市自然科学基金;

关键词：

HIV-1; Integrase; Inhibitor; 1,3-Diketo; Polyhydroxylated aromatics; Strand transfer; VIRUS TYPE-1 INTEGRASE; ONE-POT SYNTHESIS; STRAND-TRANSFER; POLYHYDROXYLATED AROMATICS; PREVENT INTEGRATION; ACID; REPLICATION; MECHANISM; NITROGEN; PLATFORM;

D O I：

10.1016/j.bmc.2011.11.014

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of novel beta-diketo derivatives which combined the virtues of 1,3-diketo, 1,2,3-triazole and polyhydroxylated aromatics moieties, were designed and synthesized as potential HIV-1 integrase (IN) inhibitors and evaluated their inhibition to the strand transfer process of HIV-1 integrase. The result indicates that 3,4,5-trihydroxylated aromatic derivatives exhibit good inhibition to HIV-1 integrase, but dihydroxylated aromatic derivatives and corresponding methoxy aromatic derivatives appear little inhibition to HIV-1 integrase. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：177 / 182

页数：6

共 21 条

[1] 1,2,3-TRIAZOLE-[2',5'-BIS-O-(TERT-BUTYLDIMETHYLSILYL)-BETA-D-RIBOFURANOSYL]-3'-SPIRO-5''-(4''-AMINO-1'',2''-OXATHIOL 2'',2''-DIOXIDE) (TSAO) ANALOGS - SYNTHESIS AND ANTI-HIV-1 ACTIVITY [J].

ALVAREZ, R ;

VELAZQUEZ, S ;

SANFELIX, A ;

AQUARO, S ;

DECLERCQ, E ;

PERNO, CF ;

KARLSSON, A ;

BALZARINI, J ;

CAMARASA, MJ .

JOURNAL OF MEDICINAL CHEMISTRY, 1994, 37 (24) :4185-4194

[2] Efficient conversion of aromatic amines into azides: A one-pot synthesis of triazole linkages [J].

Barral, Karine ;

Moorhouse, Adam D. ;

Moses, John E. .

ORGANIC LETTERS, 2007, 9 (09) :1809-1811

[3] Pharmacophore-based design of HIV-1 integrase strand-transfer inhibitors [J].

Barreca, ML ;

Ferro, S ;

Rao, A ;

De Luca, L ;

Zappalà, M ;

Monforte, AM ;

Debyser, Z ;

Witvrouw, M ;

Chimirri, A .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (22) :7084-7088

[4]

Billich A., 2003, CURR OPIN INVEST DR, V4, P206

[5] Design, Synthesis, and Biological Evaluation of Novel Hybrid Dicaffeoyltartaric/Diketo Acid and Tetrazole-Substituted L-Chicoric Acid Analogue Inhibitors of Human Immunodeficiency Virus Type 1 Integrase [J].

Crosby, David C. ;

Lei, Xiangyang ;

Gibbs, Charles G. ;

McDougall, Brenda R. ;

Robinson, W. Edward, Jr. ;

Reinecke, Manfred G. .

JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (22) :8161-8175

[6] HIV-1 integrase inhibitors: An emerging clinical reality [J].

Dayam R. ;

Al-Mawsawi L.Q. ;

Neamati N. .

Drugs in R & D, 2007, 8 (3) :155-168

[7] A Copper(I)-Catalyzed 1,2,3-Triazole Azide-Alkyne Click Compound Is a Potent Inhibitor of a Multidrug-Resistant HIV-1 Protease Variant [J].

Giffin, Michael J. ;

Heaslet, Holly ;

Brik, Ashraf ;

Lin, Ying-Chuan ;

Cauvi, Gabrielle ;

Wong, Chi-Huey ;

McRee, Duncan E. ;

Elder, John H. ;

Stout, C. David ;

Torbett, Bruce E. .

JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (20) :6263-6270

[8] 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

[9] Diketo acid inhibitor mechanism and HIV-1 integrase: Implications for metal binding in the active site of phosphotransferase enzymes [J].

Grobler, JA ;

Stillmock, K ;

Hu, BH ;

Witmer, M ;

Felock, P ;

Espeseth, AS ;

Wolfe, A ;

Egbertson, M ;

Bourgeois, M ;

Melamed, J ;

Wai, JS ;

Young, S ;

Vacca, J ;

Hazuda, DJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (10) :6661-6666

[10] 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

← 1 2 3 →