کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1392895 | 1501163 | 2012 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Chiral resolution, absolute configuration assignment and biological activity of racemic diarylpyrimidine CH(OH)-DAPY as potent nonnucleoside HIV-1 reverse transcriptase inhibitors Chiral resolution, absolute configuration assignment and biological activity of racemic diarylpyrimidine CH(OH)-DAPY as potent nonnucleoside HIV-1 reverse transcriptase inhibitors](/preview/png/1392895.png)
(+)-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 EC50 of 5.3 nM 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.
Graphical AbstractDiarylpyrimidines (+)-3a and (−)-3a were separated from racemate (±)-3a, assigned for their absolute configurations, and evaluated for their anti-HIV activity.Figure optionsDownload as PowerPoint slideHighlights
► Diarylpyrimidines (+)- and (−)-3a were separated from (±)-3a.
► The absolute configurations of (+)- and (−)-3a were confirmed by ECD spectroscopy.
► (+)-(R)-3a and (−)-(S)-3a were evaluated for their anti-HIV activity.
Journal: European Journal of Medicinal Chemistry - Volume 53, July 2012, Pages 229–234