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Discovery of novel pan-genotypic HCV NS5A inhibitors containing a novel tetracyclic core.

Abstract：

:A series of novel tetracyclic core-containing HCV NS5A inhibitors has been discovered. Incorporation of tetrahydropyran-substituted amino acid moiety improved their potency and yielded HCV NS5A inhibitors with a minimum potency shift from the GT1a strain compared to other genotypes and mutants. Compounds 53 and 54 showed the best potency profile and had reasonable half-times in rat PK studies. However, further optimization of their oral bioavailability is still needed in order to advance them for further development. [BMCL ABSTRACT] ©2000 Elsevier Science Ltd. All rights reserved.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Yu W,Hu B,Zhong B,Hao J,Lei Z,Agrawal S,Rokosz L,Liu R,Chen S,Asante-Appiah E,Kozlowski JA

doi

10.1016/j.bmcl.2019.01.031

subject

Has Abstract

pub_date

2019-03-01 00:00:00

pages

700-706

issue

5

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(19)30052-6

journal_volume

29

pub_type

杂志文章

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