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Title: Novel piperidinylamino-diarylpyrimidine derivatives with dual structural conformations as potent HIV-1 non-nucleoside reverse transcriptase inhibitors
Authors: Chen, Xuwang ×
Liu, Xin
Meng, Qing
Wang, Ding
Liu, Huiqing
De Clercq, Erik
Pannecouque, Christophe
Balzarini, Jan
Liu, Xinyong #
Issue Date: Nov-2013
Publisher: Pergamon Press
Series Title: Bioorganic & Medicinal Chemistry Letters vol:23 issue:24 pages:6593-6597
Article number: S0960-894X(13)01265-1
Abstract: A series of novel piperidinylamino-diarylpyrimidine (pDAPY) derivatives with dual structural conformations was designed through a molecular hybridization strategy and expected to bind into the non-nucleoside inhibitor binding pocket (NNIBP) of HIV-1 RT in a flexible manner. A cell-based antiviral screening assay showed that some compounds were active against both wild-type and drug-resistant mutant virus strains (K103N+Y181C RT) of HIV-1 (compound 10b3 with EC50=0.047 and 4.6μM, selectivity index=2145 and 22, respectively). Molecular simulation studies indicated that compound 10b3 could maintain the key hydrophobic interaction and hydrogen bonds with the NNIBP of two RT/ligand complexes. In particular, it could simultaneously occupy the protein/solvent interface and the entrance channel. Exploring these hybrid molecules with dual binding conformations might provide optional chemical scaffolds as novel HIV-1 reverse transcriptase inhibitors (HIV-1 NNRTIs).
URI: 
ISSN: 0960-894X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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