Thiazolone-acylsulfonamides as novel HCV NS5B polymerase allosteric inhibitors: convergence of structure-based drug design and X-ray crystallographic study.

Abstract:

:A novel series of thiazolone-acylsulfonamides were designed as HCV NS5B polymerase allosteric inhibitors. The structure based drug designs (SBDD) were guided by docking results that revealed the potential to explore an additional pocket in the allosteric site. In particular, the designed molecules contain moieties of previously described thiazolone and a newly designed acylsulfonamide linker that is in turn connected with a substituted aromatic ring. The selected compounds were synthesized and demonstrated low muM activity. The X-ray complex structure was determined at a 2.2A resolution and converged with the SBDD principle.

journal_name

Bioorg Med Chem Lett

authors

Yan S,Appleby T,Larson G,Wu JZ,Hamatake RK,Hong Z,Yao N

doi

10.1016/j.bmcl.2007.01.024

subject

Has Abstract

pub_date

2007-04-01 00:00:00

pages

1991-5

issue

7

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(07)00072-8

journal_volume

17

pub_type

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