Development and preliminary optimization of indole-N-acetamide inhibitors of hepatitis C virus NS5B polymerase

被引：81

作者：

Harper, S ^{[1
]}

Pacini, B ^{[1
]}

Avolio, S ^{[1
]}

Di Filippo, M ^{[1
]}

Migliaccio, G ^{[1
]}

Laufer, R ^{[1
]}

De Francesco, R ^{[1
]}

Rowley, M ^{[1
]}

Narjes, F ^{[1
]}

机构：

[1] IRBM, Merck Res Labs, I-00040 Monte Porzio Catone, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 05期

关键词：

D O I：

10.1021/jm049122i

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Allosteric inhibition of the hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase enzyme has recently emerged as a viable strategy toward blocking replication of viral RNA in cell-based systems. We report here a novel class of allosteric inhibitor of NS5B that shows potent affinity for the NS5B enzyme and effective inhibition of subgenomic HCV RNA replication in HUH-7 cells. Inhibitors from this class have promising characteristics for further development as anti-HCV agents.

引用

页码：1314 / 1317

页数：4

共 19 条

[1]

Battistuzzi G, 2002, EUR J ORG CHEM, V2002, P2671

[2]

Beaulieu Pierre L, 2004, Curr Opin Investig Drugs, V5, P838

[3] Non-nucleoside inhibitors of the hepatitis C virus NS5B polymerase:: discovery and preliminary SAR of benzimidazole derivatives [J].

Beaulieu, PL ;

Bös, M ;

Bousquet, Y ;

Fazal, G ;

Gauthier, J ;

Gillard, J ;

Goulet, S ;

LaPlante, S ;

Poupart, MA ;

Lefebvre, S ;

McKercher, G ;

Pellerin, C ;

Austel, V ;

Kukolj, G .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (01) :119-124

[4]

Beaulieu PL, 2003, SYNTHESIS-STUTTGART, P1683

[5] Inhibition of hepatitis C virus RNA replication by 2′-modified nucleoside analogs [J].

Carroll, SS ;

Tomassini, JE ;

Bosserman, M ;

Getty, K ;

Stahlhut, MW ;

Eldrup, AB ;

Bhat, B ;

Hall, D ;

Simcoe, AL ;

LaFemina, R ;

Rutkowski, CA ;

Wolanski, B ;

Yang, ZC ;

Migliaccio, G ;

De Francesco, R ;

Kuo, LC ;

MacCoss, M ;

Olsen, DB .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (14) :11979-11984

[6] The scientific challenge of hepatitis C [J].

Cohen, J .

SCIENCE, 1999, 285 (5424) :26-30

[7]

Dymock B W, 2001, Expert Opin Emerg Drugs, V6, P13, DOI 10.1517/14728214.6.1.13

[8]

Lesburg CA, 1999, NAT STRUCT BIOL, V6, P937

[9] Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings [J].

Lipinski, CA ;

Lombardo, F ;

Dominy, BW ;

Feeney, PJ .

ADVANCED DRUG DELIVERY REVIEWS, 1997, 23 (1-3) :3-25

[10] Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line [J].

Lohmann, V ;

Körner, F ;

Koch, JO ;

Herian, U ;

Theilmann, L ;

Bartenschlager, R .

SCIENCE, 1999, 285 (5424) :110-113

← 1 2 →