(+/-)-4-((4-((2-chlorophenyl)(hydroxy)methyl)pyrimidin-2-yl)amino)benzonitrile | 1334320-45-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (+/-)-4-((4-((2-chlorophenyl)(hydroxy)methyl)pyrimidin-2-yl)amino)benzonitrile
• 英文别名: 4-[[4-[(2-Chlorophenyl)-hydroxy-methyl]pyrimidin-2-yl]amino]benzonitrile；4-[[4-[(2-chlorophenyl)-hydroxymethyl]pyrimidin-2-yl]amino]benzonitrile
• CAS: 1334320-45-4
• 化学式: C₁₈H₁₃ClN₄O
• 分子量: 336.78
• InChiKey: XQMJLGLPGJBACD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  81.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (+/-)-4-((4-((2-chlorophenyl)(hydroxy)methyl)pyrimidin-2-yl)amino)benzonitrile 在 Diacel chiralcel OD-H 作用下， 以 乙醇 、 二氧化碳 为溶剂， 生成 (+)-(R)-4-((4-((2-chlorophenyl)(hydroxy)methyl)pyrimidin-2-yl)amino)benzonitrile 、 (-)-(S)-4-((4-((2-chlorophenyl)(hydroxy)methyl)pyrimidin-2-yl)amino)benzonitrile
  参考文献：
  名称：

  外消旋二芳基嘧啶CH（OH）-DAPY作为有效的非核苷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

  摘要：

  通过对映体过量（ee％）> 99％和纯度> 99％的超临界流体色谱（SCF）的手性技术成功地将（+）- 3a和（-）- 3a与外消旋物（±）-3a分离并分配分别通过实验性电子圆二色性（ECD）光谱和模拟的ECD光谱将它们的绝对构型分别定义为R和S，并通过时变密度泛函理论（TDDFT）计算得出。（+）-（R）-3a对野生型HIV-1表现出优异的活性，EC 50为5.3 nM，是（-）-（S）-3a效力的12倍。但是，（-）-（小号） -图3a显示出比更高的效力（+） - （[R ）- 3a中针对双HIV-1 RT突变体（K103N + Y181C）以及HIV-2 ROD应变。通过分子对接来解释（R）-和（S）-3a抗HIV-1活性差异的可能原因。

  DOI：

  10.1016/j.ejmech.2012.04.004
• 作为产物：
  描述：

  邻氯苯乙腈 在 钾硼氢 、 氧气 、 sodium hydride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 2.0h， 生成 (+/-)-4-((4-((2-chlorophenyl)(hydroxy)methyl)pyrimidin-2-yl)amino)benzonitrile
  参考文献：
  名称：

  Synthesis and structure–activity relationship of novel diarylpyrimidines with hydromethyl linker (CH(OH)-DAPYs) as HIV-1 NNRTIs

  摘要：

  A series of 26 diarylpyrimidines, characterized by the hydroxymethyl linker between the left wing benzene ring and the central pyrimidine, were synthesized and evaluated for in vitro anti-HIV activity. Most of the compounds exhibited moderate to excellent activities against wild-type HIV-1. Among them, compound 10i, bearing a chlorine atom at the C-2 position of left benzene ring, was the best congener and showed potent activity against wild-type HIV-1 with an EC50 value of 0.009 mu M, along with moderate activities against the double RT mutant (K103N + Y181C) HIV-1(IIIB) and HIV-2(ROD) with an EC50 value of 6.2 and 6.0 mu M, respectively. The preliminary structure-activity relationship (SAR) of this new series of compounds was also investigated. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.07.023

文献信息

• Synthesis and structure–activity relationship of novel diarylpyrimidines with hydromethyl linker (CH(OH)-DAPYs) as HIV-1 NNRTIs
  作者：Shuang-Xi Gu、Qiu-Qin He、Shi-Qiong Yang、Xiao-Dong Ma、Fen-Er Chen、Erik De Clercq、Jan Balzarini、Christophe Pannecouque

  DOI：10.1016/j.bmc.2011.07.023

  日期：2011.9

  A series of 26 diarylpyrimidines, characterized by the hydroxymethyl linker between the left wing benzene ring and the central pyrimidine, were synthesized and evaluated for in vitro anti-HIV activity. Most of the compounds exhibited moderate to excellent activities against wild-type HIV-1. Among them, compound 10i, bearing a chlorine atom at the C-2 position of left benzene ring, was the best congener and showed potent activity against wild-type HIV-1 with an EC50 value of 0.009 mu M, along with moderate activities against the double RT mutant (K103N + Y181C) HIV-1(IIIB) and HIV-2(ROD) with an EC50 value of 6.2 and 6.0 mu M, respectively. The preliminary structure-activity relationship (SAR) of this new series of compounds was also investigated. (C) 2011 Elsevier Ltd. All rights reserved.
• Chiral resolution, absolute configuration assignment and biological activity of racemic diarylpyrimidine CH(OH)-DAPY as potent nonnucleoside HIV-1 reverse transcriptase inhibitors
  作者：Shuang-Xi Gu、Zhi-Ming Li、Xiao-Dong Ma、Shi-Qiong Yang、Qiu-Qin He、Fen-Er Chen、Erik De Clercq、Jan Balzarini、Christophe Pannecouque

  DOI：10.1016/j.ejmech.2012.04.004

  日期：2012.7

  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

  通过对映体过量（ee％）> 99％和纯度> 99％的超临界流体色谱（SCF）的手性技术成功地将（+）- 3a和（-）- 3a与外消旋物（±）-3a分离并分配分别通过实验性电子圆二色性（ECD）光谱和模拟的ECD光谱将它们的绝对构型分别定义为R和S，并通过时变密度泛函理论（TDDFT）计算得出。（+）-（R）-3a对野生型HIV-1表现出优异的活性，EC 50为5.3 nM，是（-）-（S）-3a效力的12倍。但是，（-）-（小号） -图3a显示出比更高的效力（+） - （[R ）- 3a中针对双HIV-1 RT突变体（K103N + Y181C）以及HIV-2 ROD应变。通过分子对接来解释（R）-和（S）-3a抗HIV-1活性差异的可能原因。