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Identification of aryl dihydrouracil derivatives as palm initiation site inhibitors of HCV NS5B polymerase.

Abstract：

:Aryl dihydrouracil derivatives were identified from high throughput screening as potent inhibitors of HCV NS5B polymerase. The aryl dihydrouracil derivatives were shown to be non-competitive with respect to template RNA and elongation nucleotide substrates. They demonstrated genotype 1 specific activity towards HCV NS5B polymerases. Structure activity relationships and genotype specific activities of aryl dihydrouracil derivatives suggested that they bind to the palm initiation nucleotide pocket, a hypothesis which was confirmed by studies with polymerases containing mutations in various inhibitor binding sites. Therefore, aryl dihydrouracil derivatives represent a novel class of palm initiation site inhibitors of HCV NS5B polymerase.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Liu Y,Lim BH,Jiang WW,Flentge CA,Hutchinson DK,Madigan DL,Randolph JT,Wagner R,Maring CJ,Kati WM,Molla A

doi

10.1016/j.bmcl.2012.04.017

subject

Has Abstract

pub_date

2012-06-01 00:00:00

pages

3747-50

issue

11

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(12)00456-8

journal_volume

22

pub_type

杂志文章

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