methyl 2-(2,6-difluorophenyl)benzimidazole-4-carboxylate | 212503-84-9

• 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: methyl 2-(2,6-difluorophenyl)benzimidazole-4-carboxylate
• 英文别名: methyl 2-(2,6-difluorophenyl)-benzimidazole-2-carboxylate；Methyl 2-(2,6-difluorophenyl)-benzimidazole-4-carboxylate；methyl 2-(2,6-difluorophenyl)-1H-benzimidazole-4-carboxylate
• CAS: 212503-84-9
• 化学式: C₁₅H₁₀F₂N₂O₂
• 分子量: 288.253
• InChiKey: DSDZTLWLCKOECB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  55
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 2-(2,6-difluorophenyl)benzimidazole-4-carboxylate 在 羟胺 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 xylene 为溶剂， 反应 33.0h， 生成 C₂₁H₁₄F₄N₄O
  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：

  methyl N-(2,6-difluorobenzoyl)-3-nitro-2-anilinecarboxylate 在 铁粉 、 溶剂黄146 作用下， 反应 0.5h， 以71%的产率得到methyl 2-(2,6-difluorophenyl)benzimidazole-4-carboxylate
  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

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。
• [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。
• SUBSTITUTED BENZIMIDAZOLES AS NON-NUCLEOSIDE INHIBITORS OF REVERSE TRANSCRIPTASE
  申请人：THE UNITED STATES OF AMERICA, as represented by the Secretary of the Department of Health and Human Services

  公开号：EP1210336B1

  公开（公告）日：2007-04-25
• US6369235B1
  申请人：——

  公开号：US6369235B1

  公开（公告）日：2002-04-09