2,6-difluoro-N-(2-nitrophenyl)benzamide | 199594-48-4

• 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: 2,6-difluoro-N-(2-nitrophenyl)benzamide
• CAS: 199594-48-4
• 化学式: C₁₃H₈F₂N₂O₃
• 分子量: 278.215
• InChiKey: RVVBCZDWPHKYNH-UHFFFAOYSA-N

物化性质

• 熔点：
  139 °C
• 沸点：
  329.4±42.0 °C(Predicted)
• 密度：
  1.475±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  74.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,6-difluoro-N-(2-nitrophenyl)benzamide 在 吡啶 、 溴 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以50%的产率得到N-(2,6-difluorobenzoyl)-4-bromo-2-nitroaniline
  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
• 作为产物：
  描述：

  2,6-difluoro-N-phenylbenzamide 在 ammonium cerium (IV) nitrate 作用下， 以 乙腈 为溶剂， 反应 12.0h， 以74%的产率得到2,6-difluoro-N-(2-nitrophenyl)benzamide
  参考文献：
  名称：

  硝酸铈铵在温和条件下促进苯胺的高度化学和区域选择性邻硝化

  摘要：

  在温和和中性条件下，无需额外的催化剂和氧化剂，开发了一种新的实用的硝酸铈铵促进苯胺氨基甲酸酯的高度化学和区域选择性邻位硝化的策略。富电子苯胺和高度缺电子苯胺均能以优异的收率获得所需产品，并具有出色的官能团耐受性。

  DOI：

  10.1002/ejoc.202200746

文献信息

• Substituted benzimidazoles, and methods of use thereof, for the inhibition of HIV reverse transcription and for the treatment of HIV infection
  申请人：The United States of America as represented by the Department of Health and Human Services

  公开号：US06369235B1

  公开（公告）日：2002-04-09

  The present invention provides compositions and methods for the treatment of HIV infection. In particular, the present invention provides non-nucleoside inhibitors of reverse transcriptase (RT), as well as methods to treat HIV infection using these non-nucleoside inhibitors of RT. In preferred embodiments, the present invention provides a novel class of substituted benzimidazoles, effective in the inhibition of human immunodeficiency virus (HIV) RT.

  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。
• Synthesis and Biological Activity of Novel Nonnucleoside Inhibitors of HIV-1 Reverse Transcriptase. 2-Aryl-Substituted Benzimidazoles
  作者：Thomas Roth、Marshall L. Morningstar、Paul L. Boyer、Stephen H. Hughes、Robert W. Buckheit,、Christopher J. Michejda

  DOI：10.1021/jm970096g

  日期：1997.12.1

  nonnucleoside inhibitors of human immunodeficiency virus type-1 (HIV-1) reverse transcriptase (RT) active against the drug-induced mutations in RT continues to be a very important goal of AIDS research. We used a known inhibitor of HIV-1 RT, 1-(2,6-difluorophenyl)-1H,3H-thiazolo[3,4-alpha]benzimidazole (TZB), as the lead structure for drug design with the objective of making more potent inhibitors against

  对抗药物诱导的RT突变的新型人类免疫缺陷病毒1型（HIV-1）逆转录酶（RT）的非核苷抑制剂的开发仍然是艾滋病研究的一个重要目标。我们使用已知的HIV-1 RT抑制剂1-（2,6-二氟苯基）-1H，3H-噻唑并[3,4-α]苯并咪唑（TZB）作为药物设计的主要结构，目的在于制备针对野生型（WT）和变异RT的更有效抑制剂。合成了一系列结构上相关的1,2-取代的苯并咪唑，并评估了它们抑制HIV-1 WT RT体外聚合的能力。对一系列化合物进行了结构活性研究，以确定在N1和C2位置取代苯并咪唑环的最佳基团。最好的抑制剂1-（2,6-二氟苄基）-2-（2，6-二氟苯基）-4-甲基苯并咪唑（35）在体外酶分析中对HIV-1 WT RT的IC50 = 200 nM。利用HIV感染的MT-4细胞进行的细胞保护分析显示，35种具有对野生型病毒的强抗病毒活性（EC50 = 440 nM），同时对许多对非核苷
• ortho -Fluorobenzanilides and ortho -fluorothiobenzanilides: Molecular conformations and crystal packing
  作者：Teresa Olszewska、Jarosław Chojnacki、Barbara Wicher、Maria J. Milewska

  DOI：10.1016/j.jfluchem.2016.07.004

  日期：2016.11

  synthesized molecules adopt a geometry being deflected from planarity. The deflection was investigated by analysis of dihedral angles between mean planes of benzoyl, amide and aniline residues. Molecular conformation depends mainly on strong N–H⋯O bonds, although operation of N–H⋯F hydrogen bonding was observed in one case. Crystal packing is controlled mainly by interactions of the C–H⋯O type, also by

  合成了一系列的2-氟和2,6-二氟苯甲腈及其硫代苯甲酰苯胺类似物，以研究氟原子对其晶体结构和晶格中自组装的影响。单晶的X射线分析表明，合成的分子具有偏离平面度的几何形状。 通过分析苯甲酰基，酰胺和苯胺残基的平均平面之间的二面角来研究挠度。分子构象主要取决于强的NH键，尽管在一种情况下观察到了NHF氢键的作用。晶体堆积主要受C–H⋯O型相互作用的影响，也受π–π堆积的控制，在一种二氟取代的情况下，通过弱C Ar –F⋯F–C Ar卤素键的作用来控制。
• [EN] SUBSTITUTED BENZIMIDAZOLES AS NON-NUCLEOSIDE INHIBITORS OF REVERSE TRANSCRIPTASE<br/>[FR] BENZIMIDAZOLES SUBSTITUES EN TANT QU'INHIBITEURS NON NUCLEOSIDIQUES DE LA TRANSCRIPTASE INVERSE
  申请人：US HEALTH

  公开号：WO2001014343A1

  公开（公告）日：2001-03-01

  Benzimidazole derivatives substituted in position 2 by a 2,6 difluorophenyl and/or in position 1 by a 2,6-difluorobenzyl group are HIV-1 reverse transcriptase inhibitors useful in treatment of HIV infections.

  2-位置被2,6-二氟苯基和/或1-位置被2,6-二氟苄基取代的苯并咪唑衍生物是HIV-1反转录酶抑制剂，可用于治疗HIV感染。
• Substituted benzimidazoles as non-nucleoside inhibitors of reverse transcriptase
  申请人：——

  公开号：US20030191160A1

  公开（公告）日：2003-10-09

  The present invention provides compositions and methods for the treatment of HIV infection. In particular, the present invention provides non-nucleoside inhibitors of reverse transcriptase (RT), as well as methods to treat HIV infection using these non-nucleoside inhibitors of RT. In preferred embodiments, the present invention provides a novel class of substituted benzimidazoles, effective in the inhibition of human immunodeficiency virus (HIV) RT.

  本发明提供了治疗HIV感染的组合物和方法。特别是，本发明提供了反转录酶（RT）非核苷类抑制剂，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，能够有效抑制人类免疫缺陷病毒（HIV）RT。