Inhibitors of HCVNS5B polymerase:: synthesis and structure-activity relationships of N-1-heteroalkyl-4-hydroxyquinolon-3-yl-benzothiadiazines

被引：45

作者：

Pratt, JK ^{[1
]}

Donner, P ^{[1
]}

McDaniel, KF ^{[1
]}

Maring, CJ ^{[1
]}

Kati, WM ^{[1
]}

Mo, HM ^{[1
]}

Middleton, T ^{[1
]}

Liu, YY ^{[1
]}

Ng, T ^{[1
]}

Xie, QH ^{[1
]}

Zhang, R ^{[1
]}

Montgomery, D ^{[1
]}

Molla, A ^{[1
]}

Kempf, DJ ^{[1
]}

Kohlbrenner, W ^{[1
]}

机构：

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 06期

关键词：

hepatitis C; HCV; RNA dependent RNA polymerase; NS5B;

D O I：

10.1016/j.bmcl.2005.01.071

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

N-1-Alkylamino and N-1-alkyloxy-4-hydroxyquinolon-3-yl benzothiadiazines were synthesized and evaluated as inhibitors of genotype 1 HCV polymerase. The N-1-alkyloxy derivatives were not potent inhibitors, however N-1-alkylamino derivatives displayed comparable potency to carbon analogs. Analogs with aliphatic substituents were significantly more potent than those with benzylic substituents against genotype la polymerase. The most potent inhibitors contained small alkyl or carbocyclic substituents and exhibited IC50's of 50-100 and 200-400 nM against genotype 1 b and 1 a HCV polymerase, respectively. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：1577 / 1582

页数：6

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