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Synthesis and SAR of acyclic HCV NS3 protease inhibitors with novel P4-benzoxaborole moieties.

Abstract：

:We have synthesized and evaluated a new series of acyclic P4-benzoxaborole-based HCV NS3 protease inhibitors. Structure-activity relationships were investigated, leading to the identification of compounds 5g and 17 with low nanomolar potency in the enzymatic and cell-based replicon assay. The linker-truncated compound 5j was found to exhibit improved absorption and oral bioavailability in rats, suggesting that further reduction of molecular weight and polar surface area could result in improved drug-like properties of this novel series.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Li X,Zhang S,Zhang YK,Liu Y,Ding CZ,Zhou Y,Plattner JJ,Baker SJ,Bu W,Liu L,Kazmierski WM,Duan M,Grimes RM,Wright LL,Smith GK,Jarvest RL,Ji JJ,Cooper JP,Tallant MD,Crosby RM,Creech K,Ni ZJ,Zou W,Wright J

doi

10.1016/j.bmcl.2011.02.006

subject

Has Abstract

pub_date

2011-04-01 00:00:00

pages

2048-54

issue

7

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(11)00180-6

journal_volume

21

pub_type

杂志文章

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