Synthesis and SAR of novel 1,1-dialkyl-2(1H)-naphthalenones as potent HCV polymerase inhibitors

被引：28

作者：

Bosse, Todd D. ^{[1
]}

Larson, Daniel P. ^{[1
]}

Wagner, Rolf ^{[1
]}

Hutchinson, Doug K. ^{[1
]}

Rockway, Todd W. ^{[1
]}

Kati, Warren M. ^{[1
]}

Liu, Yaya ^{[1
]}

Masse, Sherie ^{[1
]}

Middleton, Tim ^{[1
]}

Mo, Hongmei ^{[1
]}

Montgomery, Debra ^{[1
]}

Jiang, Wen ^{[1
]}

Koev, Gennadly ^{[1
]}

Kempf, Dale J. ^{[1
]}

Molla, Akhter ^{[1
]}

机构：

[1] Abbott Labs, Global Pharmaceut Res & Dev, Infect Dis Res, Abbott Pk, IL 60064 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 02期

关键词：

polymerase; inhibitors; benzothiadiazines; hepatitis; HCV; naphthalenones;

D O I：

10.1016/j.bmcl.2007.11.088

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of gem-dialkyl naphthalenone derivatives with varied alkyl substitutions were synthesized and evaluated according to their structure-activity relationship. This investigation led to the discovery of potent inhibitors of the hepatitis C virus at low nanomolar concentrations in both enzymatic and cell-based HCV genotype la assays. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：568 / 570

页数：3

共 7 条

[1] Derivatives of 2,5-diaminobenzenesulfonamide [J].

Goldfarb, AR ;

Berk, B .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1943, 65 :738-739

[2] Control of hepatitis C: A medicinal chemistry perspective [J].

Gordon, CP ;

Keller, PA .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (01) :1-20

[3] Course and outcome of hepatitis C [J].

Hoofnagle, JH .

HEPATOLOGY, 2002, 36 (05) :S21-S29

[4]

Hutchinson KD, 2005, PCT Int Appl, Patent No. [WO2005019191, 2005019191]

[5] Different anti-HCV profiles of statins and their potential for combination therapy with interferon [J].

Ikeda, Masanori ;

Abe, Ken-ichi ;

Yamada, Masashi ;

Dansako, Hiromichi ;

Naka, Kazuhito ;

Kato, Nobuyuki .

HEPATOLOGY, 2006, 44 (01) :117-125

[6] Inhibitors of HCVNS5B polymerase:: synthesis and structure-activity relationships of N-1-heteroalkyl-4-hydroxyquinolon-3-yl-benzothiadiazines [J].

Pratt, JK ;

Donner, P ;

McDaniel, KF ;

Maring, CJ ;

Kati, WM ;

Mo, HM ;

Middleton, T ;

Liu, YY ;

Ng, T ;

Xie, QH ;

Zhang, R ;

Montgomery, D ;

Molla, A ;

Kempf, DJ ;

Kohlbrenner, W .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (06) :1577-1582

[7] Inhibitors of HCVNS5B polymerase:: Synthesis and structure-activity relationships of N-1-benzyl and N-1-[3-methylbutyl]-4-hydroxy-1,8-naphthyridon-3-yl benzothiadiazine analogs containing substituents on the aromatic ring [J].

Rockway, Todd W. ;

Zhang, Rong ;

Liu, Dachun ;

Betebenner, David A. ;

McDaniel, Keith F. ;

Pratt, John K. ;

Beno, David ;

Montgomery, Debra ;

Jiang, Wen W. ;

Masse, Sherie ;

Kati, Warren M. ;

Middleton, Tim ;

Molla, Akhteruzzaman ;

Maring, Clarence J. ;

Kempf, Dale J. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (14) :3833-3838

← 1 →