Title: Discovery of novel diarylpyrimidines as potent HIV NNRTIs via a structure-guided core-refining approach
Authors: Li, Xiao ×
Chen, Wenmin
Tian, Ye
Liu, Huiqing
Zhan, Peng
De Clercq, Erik
Pannecouque, Christophe
Balzarini, Jan
Liu, Xinyong #
Issue Date: May-2014
Series Title: European Journal of Medicinal Chemistry vol:80 pages:112-121
Article number: S0223-5234(14)00357-2
Abstract: Guided by crystal structures of HIV-1 RT/DAPY complex and molecular modeling studies, a series of novel DAPY derivatives were rationally designed, synthesized and evaluated for their anti-HIV activities. Among them, 16 compounds significantly inhibited HIV-1 IIIB replication with EC50 values lower than 66 nM. Particularly, compound 7a was the most potent inhibitor against HIV-1 wild-type and double RT mutant HIV-1 strain K103N/Y181C, with an EC50 value of 2.5 nM (SI = 13,740) and 0.33 μM (SI = 107), respectively. Unexpectedly, compound 8c was found to show moderate anti-HIV-2 potency (EC50 = 5.57 μM). Preliminary structure-activity relationships (SARs) and molecular modeling of these new analogues were also discussed in detail.
ISSN: 0223-5234
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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