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Inhibitors of HCV NS5B polymerase: synthesis and structure-activity relationships of N-1-heteroalkyl-4-hydroxyquinolon-3-yl-benzothiadiazines.

Abstract：

: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 1a polymerase. The most potent inhibitors contained small alkyl or carbocyclic substituents and exhibited IC50's of 50-100 and 200-400 nM against genotype 1b and 1a HCV polymerase, respectively.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Pratt JK,Donner P,McDaniel KF,Maring CJ,Kati WM,Mo H,Middleton T,Liu Y,Ng T,Xie Q,Zhang R,Montgomery D,Molla A,Kempf DJ,Kohlbrenner W

doi

10.1016/j.bmcl.2005.01.071

subject

Has Abstract

pub_date

2005-03-15 00:00:00

pages

1577-82

issue

6

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(05)00138-1

journal_volume

15

pub_type

杂志文章

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