Design and synthesis of highly potent HIV-1 protease inhibitors with novel isosorbide-derived P2 ligands
- PMID: 24767846
- DOI: 10.1016/j.bmcl.2014.04.008
Design and synthesis of highly potent HIV-1 protease inhibitors with novel isosorbide-derived P2 ligands
Abstract
The design, synthesis, and biological evaluation of a series of six HIV-1 protease inhibitors incorporating isosorbide moiety as novel P2 ligands are described. All the compounds are very potent HIV-1 protease inhibitors with IC50 values in the nanomolar or picomolar ranges (0.05-0.43 nM). Molecular docking studies revealed the formation of an extensive hydrogen-bonding network between the inhibitor and the active site. Particularly, the isosorbide-derived P2 ligand is involved in strong hydrogen bonding interactions with the backbone atoms.
Keywords: Design; Drug-resistant; HIV-1 protease inhibitors; Isosorbides; P2 ligand; Synthesis.
Copyright © 2014 Elsevier Ltd. All rights reserved.
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