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
复制标题
外消旋二芳基嘧啶 CH(OH)-DAPY 作为有效非核苷 HIV-1 逆转录酶抑制剂的手性拆分、绝对构型分配和生物活性
DOI：
10.1016/j.ejmech.2012.04.004
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发表时间：
2012-07-01
影响因子：
6.7
通讯作者：
Pannecouque, Christophe
中科院分区：
文献类型：
--
作者：
Gu, Shuang-Xi;Li, Zhi-Ming;Pannecouque, Christophe
(+)-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. (C) 2012 Elsevier Masson SAS. All rights reserved.
