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  • Title: Disubstituted Bis-THF Moieties as New P2 Ligands in Nonpeptidal HIV-1 Protease Inhibitors (II).
    Author: Hohlfeld K, Wegner JK, Kesteleyn B, Linclau B, Unge J.
    Journal: J Med Chem; 2015 May 14; 58(9):4029-38. PubMed ID: 25897791.
    Abstract:
    A series of darunavir analogues featuring a substituted bis-THF ring as P2 ligand have been synthesized and evaluated. Very high affinity protease inhibitors (PIs) with an interesting activity on wild-type HIV and a panel of multi-PI resistant HIV-1 mutants containing clinically observed, primary mutations were identified using a cell-based assay. Crystal structure analysis was conducted on a number of PI analogues in complex with HIV-1 protease.
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