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Novel, potent and orally bioavailable indolizidinone-derived inhibitors of the hepatitis C virus NS3 protease.

Abstract：

:A novel, potent, and orally bioavailable class of product-like inhibitors of the HCV NS3 protease was discovered by constraining the P2-P3 amide bond and the P3 hydrocarbon substituent to the protease-bound conformation. This preorganization was accomplished by incorporation of the P2-P3 amide into a six-membered ring attached to the P2-proline 5-position. Isothermal calorimetric characterization of the role of hydrocarbon substitution of this six-membered ring, upon binding the HCV NS3 protease, was found to be exclusively entropic in nature. The synthesis, preliminary SAR and pharmacokinetic profiling of this compact, indolizidinone-derived scaffold are described.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Clarke MO,Byun D,Chen X,Doerffler E,Leavitt SA,Sheng XC,Yang CY,Kim CU

doi

10.1016/j.bmcl.2011.11.107

subject

Has Abstract

pub_date

2012-01-15 00:00:00

pages

1095-8

issue

2

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(11)01651-9

journal_volume

22

pub_type

杂志文章

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