2-(2-chlorophenyl)-1-(1H-imidazol-1-yl)ethan-1-one

• 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: 2-(2-chlorophenyl)-1-(1H-imidazol-1-yl)ethan-1-one
• 英文别名: 2-(2-Chlorophenyl)-1-imidazol-1-ylethanone；2-(2-chlorophenyl)-1-imidazol-1-ylethanone
• 化学式: C₁₁H₉ClN₂O
• 分子量: 220.658
• InChiKey: XCRMESBIMGGAIQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  34.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(2-chlorophenyl)-1-(1H-imidazol-1-yl)ethan-1-one 在 sodium ethanolate 、 三乙胺 、 magnesium chloride 作用下， 以 乙醇 为溶剂， 反应 9.0h， 生成 6-(2-Chloro-benzyl)-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one
  参考文献：
  名称：

  5-Alkyl-2-(alkylthio)-6-(2,6-dihalophenylmethyl)-3,4-dihydropyrimidin-4(3H)-ones:  Novel Potent and Selective Dihydro-alkoxy-benzyl-oxopyrimidine Derivatives

  摘要：

  Molecular modeling analysis of compounds belonging to the recently published series of dihydroalkoxy-benzyl-oxopyrimidines (DABOs), such as S-DABOs and DATNOs, gave support to the design of new 2,6-disubstituted benzyl-DABO derivatives as highly potent and specific inhibitors of the HIV-1 reverse transcriptase (RT). To follow up on the novel DABO derivatives, we decided to investigate the effect of electron-withdrawing substituents in the benzyl unit of the S-DABO skeleton versus their anti-HIV-1 activity. Such chemical modifications impacted the inhibitory activity, especially when two halogen units were introduced at positions 2 and 6 in the phenyl portion of the benzyl group bound to C-6 of the pyrimidine ring. Various 5-alkyl-2-(alkyl(or cycloalkyl)thio)-6-(2,B-dichloro(or 2, 6-difluoro)phenylmethyl)-3,4-dihydropyrimidin-4(3H)-ones were then synthesized and tested as anti-HIV-1 agents in both cell-based and enzyme (recombinant reverse transcriptase, rRT) assays. Among the various mono- and disubstituted phenyl derivatives, the most potent were those containing a 6-(2,6-difluorophenylmethyl) substituent (F-DABOs), which showed EC50's ranging between 40 and 90 nM and selectivity indexes up to greater than or equal to 5000. An excellent correlation was found between EC50 and IC50 values which confirmed that these compounds act as inhibitors of the HIV-1 RT. The structure-activity relationships of the newly synthesized pyrimidinones are presented herein.

  DOI：

  10.1021/jm980260f
• 作为产物：
  描述：

  邻氯苯乙酸 、 N,N'-羰基二咪唑 以 二氯甲烷 为溶剂， 反应 2.0h， 以85%的产率得到2-(2-chlorophenyl)-1-(1H-imidazol-1-yl)ethan-1-one
  参考文献：
  名称：

  利用无碱乙醇酸铵中的咪唑效应：合成和机理研究

  摘要：

  在没有碱的情况下，N-酰基咪唑和催化的异硫脲盐酸盐催化物起烯醇铵的前体作用。已经进行了使用不同的α，β-不饱和Michael受体的对映选择性Michael加成环化反应，以形成具有高立体选择性的二氢吡喃酮和二氢吡啶并酮。使用RPKA进行的详细机械研究揭示了“咪唑”效应在烯醇铵形成中的重要性，并强调了与传统碱介导方法的主要区别。

  DOI：

  10.1002/anie.201608046

文献信息

• Exploiting the Imidazolium Effect in Base-free Ammonium Enolate Generation: Synthetic and Mechanistic Studies
  作者：Claire M. Young、Daniel G. Stark、Thomas H. West、James E. Taylor、Andrew D. Smith

  DOI：10.1002/anie.201608046

  日期：2016.11.7

  function as ammonium enolate precursors in the absence of base. Enantioselective Michael addition–cyclization reactions using different α,β‐unsaturated Michael acceptors have been performed to form dihydropyranones and dihydropyridinones with high stereoselectivity. Detailed mechanistic studies using RPKA have revealed the importance of the “imidazolium” effect in ammonium enolate formation and have highlighted

  在没有碱的情况下，N-酰基咪唑和催化的异硫脲盐酸盐催化物起烯醇铵的前体作用。已经进行了使用不同的α，β-不饱和Michael受体的对映选择性Michael加成环化反应，以形成具有高立体选择性的二氢吡喃酮和二氢吡啶并酮。使用RPKA进行的详细机械研究揭示了“咪唑”效应在烯醇铵形成中的重要性，并强调了与传统碱介导方法的主要区别。
• 5-Alkyl-2-(alkylthio)-6-(2,6-dihalophenylmethyl)-3,4-dihydropyrimidin-4(3<i>H</i>)-ones:  Novel Potent and Selective Dihydro-alkoxy-benzyl-oxopyrimidine Derivatives
  作者：Antonello Mai、Marino Artico、Gianluca Sbardella、Silvio Massa、Ettore Novellino、Giovanni Greco、Anna Giulia Loi、Enzo Tramontano、Maria Elena Marongiu、Paolo La Colla

  DOI：10.1021/jm980260f

  日期：1999.2.1

  Molecular modeling analysis of compounds belonging to the recently published series of dihydroalkoxy-benzyl-oxopyrimidines (DABOs), such as S-DABOs and DATNOs, gave support to the design of new 2,6-disubstituted benzyl-DABO derivatives as highly potent and specific inhibitors of the HIV-1 reverse transcriptase (RT). To follow up on the novel DABO derivatives, we decided to investigate the effect of electron-withdrawing substituents in the benzyl unit of the S-DABO skeleton versus their anti-HIV-1 activity. Such chemical modifications impacted the inhibitory activity, especially when two halogen units were introduced at positions 2 and 6 in the phenyl portion of the benzyl group bound to C-6 of the pyrimidine ring. Various 5-alkyl-2-(alkyl(or cycloalkyl)thio)-6-(2,B-dichloro(or 2, 6-difluoro)phenylmethyl)-3,4-dihydropyrimidin-4(3H)-ones were then synthesized and tested as anti-HIV-1 agents in both cell-based and enzyme (recombinant reverse transcriptase, rRT) assays. Among the various mono- and disubstituted phenyl derivatives, the most potent were those containing a 6-(2,6-difluorophenylmethyl) substituent (F-DABOs), which showed EC50's ranging between 40 and 90 nM and selectivity indexes up to greater than or equal to 5000. An excellent correlation was found between EC50 and IC50 values which confirmed that these compounds act as inhibitors of the HIV-1 RT. The structure-activity relationships of the newly synthesized pyrimidinones are presented herein.