Title: Chiral resolution, absolute configuration assignment and biological activity of racemic diarylpyrimidine CH(OH)-DAPY as potent nonnucleoside HIV-1 reverse transcriptase inhibitors
Authors: Gu, S-X ×
Li, Z-M
Ma, X-D
Yang, S-Q
He, Q-Q
Chen, F-E
De Clercq, Erik
Balzarini, Jan
Pannecouque, Christophe #
Issue Date: Jul-2012
Series Title: European Journal of Medicinal Chemistry vol:53 pages:229-234
Abstract: (+)-3a and (-)-3a were successfully separated from racemate (±)-3a by the chiral technique of supercritical fluid chromatography (SCF) with enantiomeric excess (ee%) >99% and purity >99%, and assigned for their absolute configuration as R and S, respectively, by the experimental electronic circular dichroism (ECD) spectrum and simulated ECD spectra calculated by time-dependent density functional theory (TDDFT) calculations. (+)-(R)-3a displayed excellent activity with an EC(50) of 5.3nM against wild-type HIV-1, which was 12-fold more potent than (-)-(S)-3a. However, (-)-(S)-3a showed higher potency than (+)-(R)-3a against the double HIV-1 RT mutant (K103N+Y181C) as well as HIV-2 strain ROD. The possible reason for the difference of (R)- and (S)-3a in anti-HIV-1 activity was interpreted by molecular docking.
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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