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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 (0.05–0.43nM). Molecular docking studies revealed the formation of an extensive hydrogen-bonding network between the inhibitor...
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