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Design and synthesis of potent HIV-1 protease inhibitors incorporating hydroxyprolinamides as novel P2 ligands.

Abstract：

:A series of new HIV-1 protease inhibitors with the hydroxyethylamine core and different hydroxyprolinamide P2 ligands were designed and synthesized. Variation of substitutions at the P2 significantly affected the enzyme inhibitory potency of the inhibitors. Compounds 2a and 2d showed excellent enzyme inhibitory activity with IC(50) values in the nanomolar range. An active site binding model for inhibitors 2a and 2d was suggested based upon the computational-docking results of the ligand with HIV-1 protease. This model offers molecular insights regarding ligand-binding site interactions of the hydroxyprolinamide-derived novel P2-ligand.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Gao BL,Zhang CM,Yin YZ,Tang LQ,Liu ZP

doi

10.1016/j.bmcl.2011.04.070

subject

Has Abstract

pub_date

2011-06-15 00:00:00

pages

3730-3

issue

12

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(11)00529-4

journal_volume

21

pub_type

杂志文章

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