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P4 and P1' optimization of bicycloproline P2 bearing tetrapeptidyl alpha-ketoamides as HCV protease inhibitors.

Abstract：

:With the aim of improving HCV protease inhibitors reported in our previous manuscripts, we synthesized and evaluated a series of 1a-based tetrapeptidyl alpha-ketoamides with additional P4 modification. The promising analog discovered through this SAR, 5a, was further derivatized at P1' or P1 position. As a result of these efforts, we found that replacement of the P4 valine as seen in 1a with cyclohexylglycine (Chg) resulted in the discovery of 5a, 5c, and 5e endowed with improved cellular activity in comparison to 1a.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Yip Y,Victor F,Lamar J,Johnson R,Wang QM,Glass JI,Yumibe N,Wakulchik M,Munroe J,Chen SH

doi

10.1016/j.bmcl.2004.07.007

subject

Has Abstract

pub_date

2004-10-04 00:00:00

pages

5007-11

issue

19

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(04)00896-0

journal_volume

14

pub_type

杂志文章

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