当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Discovery of tricyclic 5,6-dihydro-1H-pyridin-2-ones as novel, potent, and orally bioavailable inhibitors of HCV NS5B polymerase.

Discovery of tricyclic 5,6-dihydro-1H-pyridin-2-ones as novel, potent, and orally bioavailable inhibitors of HCV NS5B polymerase.

Abstract：

:A novel series of non-nucleoside small molecules containing a tricyclic dihydropyridinone structural motif was identified as potent HCV NS5B polymerase inhibitors. Driven by structure-based design and building on our previous efforts in related series of molecules, we undertook extensive SAR studies, in which we identified a number of metabolically stable and very potent compounds in genotype 1a and 1b replicon assays. This work culminated in the discovery of several inhibitors, which combined potent in vitro antiviral activity against both 1a and 1b genotypes, metabolic stability, good oral bioavailability, and high C(12) (PO)/EC(50) ratios.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Ruebsam F,Murphy DE,Tran CV,Li LS,Zhao J,Dragovich PS,McGuire HM,Xiang AX,Sun Z,Ayida BK,Blazel JK,Kim SH,Zhou Y,Han Q,Kissinger CR,Webber SE,Showalter RE,Shah AM,Tsan M,Patel RA,Thompson PA,Lebrun LA,Hou HJ,

doi

10.1016/j.bmcl.2009.09.045

subject

Has Abstract

pub_date

2009-11-15 00:00:00

pages

6404-12

issue

22

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(09)01302-X

journal_volume

19

pub_type

杂志文章

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