2-Chloro-1-[(3,4-difluorophenyl)methyl]benzimidazole | 388574-66-1

• 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: 2-Chloro-1-[(3,4-difluorophenyl)methyl]benzimidazole
• CAS: 388574-66-1
• 化学式: C₁₄H₉ClF₂N₂
• 分子量: 278.689
• InChiKey: NHWTUJYPKCJPCM-UHFFFAOYSA-N

物化性质

• 沸点：
  430.7±55.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  17.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-Chloro-1-[(3,4-difluorophenyl)methyl]benzimidazole 在 一水合肼 作用下， 反应 5.0h， 以90%的产率得到[1-[(3,4-Difluorophenyl)methyl]benzimidazol-2-yl]hydrazine
  参考文献：
  名称：

  [1,2,4]Triazino[4,3-a]benzimidazole Acetic Acid Derivatives:  A New Class of Selective Aldose Reductase Inhibitors

  摘要：

  Acetic acid derivatives of [1,2,4]triazino[4,3-alpha ]benzimidazole (TBI) were synthesized and tested in vitro and in vivo as a novel class of aldose reductase (ALR2) inhibitors. Compound 3, (10-benzyl[1,2,4]triazino[4,3-alpha ]benzimidazol-3,4(10H)-dion-2-yl)acetic acid, displayed the highest inhibitory activity (IC50 = 0.36 muM) and was found to be effective in preventing cataract development in severely galactosemic rats when administered as an eyedrop solution. All the compounds investigated were selective for ALR2, since none of them inhibited appreciably aldehyde reductase, sorbitol dehydrogenase, or glutathione reductase. The activity of 3 was lowered by inserting various substituents on the pendant phenyl ring, by shifting the acetic acid moiety from the 2 to the 3 position of the TBI nucleus, or by cleaving the TBI system to yield benzimidazolylidenehydrazines as open-chain analogues. A three-dimensional model of human ALR2 was built, taking into account the conformational. changes induced by the binding of inhibitors such as zopolrestat, to simulate the docking of 3 into the enzyme active site. The theoretical binding mode of 3 was fully consistent with the structure-activity relationships in the TBI series and will guide the design of novel ALR2 inhibitors.

  DOI：

  10.1021/jm0109210
• 作为产物：
  描述：

  3,4-二氟溴苄 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 2-Chloro-1-[(3,4-difluorophenyl)methyl]benzimidazole
  参考文献：
  名称：

  WO2006/74991

  摘要：

  公开号：

文献信息

• Novel 2-Amino Benzimidazole Derivatives and Their Use As Modulators Of Small-Conductance Calcium-Activated Potassium Channels
  申请人：Sorensen Ulrik Svane

  公开号：US20080200529A1

  公开（公告）日：2008-08-21

  This invention relates to novel 2-amino benzimidazole derivatives useful as modulators of small-conductance calcium-activated potassium channels (SK channels). In other aspects the invention relates to the use of these compounds in a method for therapy and to pharmaceutical compositions comprising the compounds of the invention.

  本发明涉及一种新型2-氨基苯并咪唑衍生物，可用作小通量钙激活钾通道（SK通道）的调节剂。在其他方面，本发明涉及将这些化合物用于治疗方法以及包含本发明化合物的制药组合物。
• COMBINATIONS OF MONOAMINE REUPTAKE INHIBITORS AND POTASSIUM CHANNEL ACTIVATORS
  申请人：Sorensen Ulrik Svane

  公开号：US20090239880A1

  公开（公告）日：2009-09-24

  This invention provides pharmaceutical compositions comprising therapeutically effective amounts of a monoamine reuptake inhibitor and an SK inhibitor. In another aspect the invention provides novel benzoimidazole derivatives for use according to the invention.

  该发明提供了药物组合物，包括治疗有效量的单胺再摄取抑制剂和SK抑制剂。在另一个方面，该发明提供了用于该发明的新型苯并咪唑衍生物。
• MEDICINAL USE OF RECEPTOR LIGANDS
  申请人：Receveur Jean-Marie

  公开号：US20090062317A1

  公开（公告）日：2009-03-05

  Compounds of formula (I) are ligands of the melanin concentrating hormone-1 receptor (MCH-1R), useful in the treatment of diseases responsive to modulation of melanin concentrating hormone (MCH) activity, for example feeding disorders and diseases for which obesity is a risk factor (I): wherein ring B is selected from specific substituted phenyl or benz-fused 5 membered N-containing heterocycles defined in the specification; R, is attached to a ring carbon of ring B, and represents hydrogen, F, Cl, or —OCH 3 ; X is ═CH— or ═N—; L, is —CH 2 — or —CH 2 CH 2 —; L 2 is a bond, —CH 2 — or —CO—; R2 is H or C, —C 3 alkyl, or —N(R 2 ) L, —is selected from specific cyclic amino linker radicals as defined in the specification; ring A is selected from specific N-containing heterocyclic rings as defined in the specification.

  式(I)的化合物是黑素浓集激素-1受体(MCH-1R)的配体，可用于治疗对黑素浓集激素(MCH)活性调节敏感的疾病，例如进食障碍和肥胖是危险因素的疾病（式(I)）：其中环B选自规定的特定取代苯基或苯并5元杂环；R附着在环B的环碳上，表示氢，F，Cl或—OCH3；X为═CH—或═N—；L为—CH2—或—CH2CH2—；L2为键，—CH2—或—CO—；R2为H或C，—C3烷基，或—N(R2)L，—选自规定的特定环状氨基连接基团。环A选自规定的特定含氮杂环。
• NOVEL 2-AMINO BENZIMIDAZOLE DERIVATIVES AND THEIR USE AS MODULATORS OF SMALL-CONDUCTANCE CALCIUM-ACTIVATED POTASSIUM CHANNELS
  申请人：Sørensen Ulrik Svane

  公开号：US20100280087A1

  公开（公告）日：2010-11-04

  This invention relates to novel 2-amino benzimidazole derivatives useful as modulators of small-conductance calcium-activated potassium channels (SK channels). In other aspects the invention relates to the use of these compounds in a method for therapy and to pharmaceutical compositions comprising the compounds of the invention.

  本发明涉及新颖的2-氨基苯并咪唑衍生物，其可用作小电导钙激活钾通道（SK通道）的调节剂。在其他方面，本发明涉及使用这些化合物的方法进行治疗，并且涉及包含本发明化合物的制药组合物。
• Novel 2-amino benzimidazole derivatives and their use as modulators of small-conductance calcium-activated potassium channels.
  申请人：NeuroSearch AS

  公开号：EP2319512A1

  公开（公告）日：2011-05-11

  This invention relates to novel 2-amino benzimidazole derivatives of formula (Ia) and (Ib) useful as modulators of small-conductance calcium-activated potassium channels (SK channels). In other aspects the invention relates to the use of these compounds in a method for therapy and to pharmaceutical compositions comprising the compounds of the invention.

  本发明涉及新型的式(Ia)和(Ib)2-氨基苯并咪唑衍生物，可作为小电导钙激活钾通道（SK 通道）的调节剂。 在其他方面，本发明涉及这些化合物在治疗方法中的用途以及包含本发明化合物的药物组合物。