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3-heterocyclyl quinolone inhibitors of the HCV NS5B polymerase.

Abstract：

:The discovery and optimization of a novel class of quinolone small-molecules that inhibit NS5B polymerase, a key enzyme of the HCV viral life-cycle, is described. Our research led to the replacement of a hydrolytically labile ester functionality with bio-isosteric heterocycles. An X-ray crystal structure of a key analog bound to NS5B facilitated the optimization of this series of compounds to afford increased activity against the target enzyme and in the cell-based replicon assay system.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Kumar DV,Rai R,Brameld KA,Riggs J,Somoza JR,Rajagopalan R,Janc JW,Xia YM,Ton TL,Hu H,Lehoux I,Ho JD,Young WB,Hart B,Green MJ

doi

10.1016/j.bmcl.2011.11.013

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

300-4

issue

1

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(11)01545-9

journal_volume

22

pub_type

杂志文章

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