Literature

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.

DOI： 10.1016/j.bmcl.2011.04.070

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

Bioorganic & Medicinal Chemistry Letters 2011.0

Design, synthesis, and X-ray studies of potent HIV-1 protease inhibitors incorporating aminothiochromane and aminotetrahydronaphthalene carboxamide derivatives as the P2 ligands

European Journal of Medicinal Chemistry 2018.0

Design and Synthesis of Potent HIV-1 Protease Inhibitors Incorporating Hexahydrofuropyranol-Derived High Affinity P<sub>2</sub> Ligands: Structure−Activity Studies and Biological Evaluation

Journal of Medicinal Chemistry 2011.0

Design and synthesis of highly potent HIV-1 protease inhibitors with novel isosorbide-derived P2 ligands

Bioorganic & Medicinal Chemistry Letters 2014.0

Highly Potent HIV-1 Protease Inhibitors with Novel Tricyclic P2 Ligands: Design, Synthesis, and Protein–Ligand X-ray Studies

Journal of Medicinal Chemistry 2013.0

Design of HIV-1 Protease Inhibitors with Pyrrolidinones and Oxazolidinones as Novel P1′-Ligands To Enhance Backbone-Binding Interactions with Protease: Synthesis, Biological Evaluation, and Protein−Ligand X-ray Studies