N-1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)-benzimidazol-4-methyl-acetamide | 327619-55-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: N-1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)-benzimidazol-4-methyl-acetamide
• 英文别名: N-[[2-(2,6-difluorophenyl)-1-[(2,6-difluorophenyl)methyl]benzimidazol-4-yl]methyl]acetamide
• CAS: 327619-55-6
• 化学式: C₂₃H₁₇F₄N₃O
• 分子量: 427.401
• InChiKey: QSBVMKCHOMJCFO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  46.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)-benzimidazol-4-methyl-acetamide 、 碘甲烷 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 以94%的产率得到1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)-4-(N-acetyl-N-methyl)-aminometylbenzimidazole
  参考文献：
  名称：

  Substituted benzimidazoles, and methods of use thereof, for the inhibition of HIV reverse transcription and for the treatment of HIV infection

  摘要：

  本发明提供了用于治疗HIV感染的组合物和方法。具体来说，本发明提供了非核苷类逆转录酶（RT）抑制剂，以及使用这些非核苷类RT抑制剂治疗HIV感染的方法。在优选实施例中，本发明提供了一类新型的取代苯并咪唑化合物，对人类免疫缺陷病毒（HIV）RT的抑制效果显著。

  公开号：

  US06369235B1
• 作为产物：
  描述：

  1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)-4-chloromethylbenzimidazole 在 sodium azide 、 溶剂黄146 、 三乙胺 、 锌 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 N-1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)-benzimidazol-4-methyl-acetamide
  参考文献：
  名称：

  Synthesis, Biological Activity, and Crystal Structure of Potent Nonnucleoside Inhibitors of HIV-1 Reverse Transcriptase That Retain Activity against Mutant Forms of the Enzyme

  摘要：

  In an ongoing effort to develop novel and potent nonnucleoside HIV-1 reverse transcriptase (RT) inhibitors that are effective against the wild type (WT) virus and clinically observed mutants, 1,2-bis-substituted benzimidazoles were synthesized and tested. Optimization of the N1 and C2 positions of benzimidazole led to the development of 1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)-4-methylbenzimidazole (1) (IC50 = 0.2 mu M, EC50 = 0.44 mu M, and TC50 >= 100 against WT). This paper describes how substitution on the benzimidazole ring profoundly affects activity. Substituents at the benzimidazole C4 dramatically enhanced potency, while at C5 or C6 substituents were generally detrimental or neutral to activity, respectively. A 7-methyl analogue did not inhibit HIV-1 RT. Determination of the crystal structure of 1 bound to RT provided the basis for accurate modeling of additional analogues, which were synthesized and tested. Several derivatives were nanomolar inhibitors of wild-type virus and were effective against clinically relevant HIV-1 mutants.

  DOI：

  10.1021/jm060103d