(E)-5-bromo-2-[2-(4-tert-butylphenyl)vinyl]-1H-benzoimidazole | 956282-58-9

• 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: (E)-5-bromo-2-[2-(4-tert-butylphenyl)vinyl]-1H-benzoimidazole
• 英文别名: (E)-5-bromo-2-[2-(4-tert-butyl-phenyl)-vinyl]-1H-benzimidazole；6-bromo-2-[(E)-2-(4-tert-butylphenyl)ethenyl]-1H-benzimidazole
• CAS: 956282-58-9
• 化学式: C₁₉H₁₉BrN₂
• 分子量: 355.277
• InChiKey: JWGPMLBFHXFLGP-IZZDOVSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  28.7
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (E)-5-bromo-2-[2-(4-tert-butylphenyl)vinyl]-1H-benzoimidazole 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium tetrahydroborate 、 caesium carbonate 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 21.0h， 生成 (E)-1-(2-{2-[2-(4-tert-butylphenyl)vinyl]-1H-benzoimidazol-5-yl}phenyl)ethanol
  参考文献：
  名称：

  Benzo[d]imidazole Transient Receptor Potential Vanilloid 1 Antagonists for the Treatment of Pain: Discovery of trans-2-(2-{2-[2-(4-Trifluoromethyl-phenyl)-vinyl]-1H-benzimidazol-5-yl}-phenyl)-propan-2-ol (Mavatrep)

  摘要：

  Reported herein is the design, synthesis, and Pharmacologic characterization of a class of TRPV1 antagonists constructed on a benzo[d]imidazole platform that evolved from a biaryl amide lead. This design composes three sections: a 2-substituted 5-phenyl headgroup attached to the benzo [d]imidazole platform, which is tethered at the two position to a phenyl tail group. Optimization of this design led to the identification of 4 (mavatrep), comprising a trifluoromethyl-phenyl-vinyl tail. In a TRPV1 functional assay, using cells expressing recombinant human TRPV1 channels, 4 antagonized capsaicin-induced Ca2+ influx, with an IC50 value of 4.6 nM. In the complete Freund's adjuvant- and carrageenan-induced thermal hypersensitivity models, 4 exhibited full efficacy, With ED80 values of 7.8 and 0.5 mg/kg, respectively, corresponding to plasma levels of 270.8 and 9.2 ng/mL, respectively. On the basis of its superior pharmacologic and safety profile, 4 (mavatrep) was selected for clinical development for the treatment of pain.

  DOI：

  10.1021/acs.jmedchem.5b00132
• 作为产物：
  描述：

  4-tert-butyl-trans-cinnamic acid 在 草酰氯 、 溶剂黄146 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 生成 (E)-5-bromo-2-[2-(4-tert-butylphenyl)vinyl]-1H-benzoimidazole
  参考文献：
  名称：

  Benzo[d]imidazole Transient Receptor Potential Vanilloid 1 Antagonists for the Treatment of Pain: Discovery of trans-2-(2-{2-[2-(4-Trifluoromethyl-phenyl)-vinyl]-1H-benzimidazol-5-yl}-phenyl)-propan-2-ol (Mavatrep)

  摘要：

  Reported herein is the design, synthesis, and Pharmacologic characterization of a class of TRPV1 antagonists constructed on a benzo[d]imidazole platform that evolved from a biaryl amide lead. This design composes three sections: a 2-substituted 5-phenyl headgroup attached to the benzo [d]imidazole platform, which is tethered at the two position to a phenyl tail group. Optimization of this design led to the identification of 4 (mavatrep), comprising a trifluoromethyl-phenyl-vinyl tail. In a TRPV1 functional assay, using cells expressing recombinant human TRPV1 channels, 4 antagonized capsaicin-induced Ca2+ influx, with an IC50 value of 4.6 nM. In the complete Freund's adjuvant- and carrageenan-induced thermal hypersensitivity models, 4 exhibited full efficacy, With ED80 values of 7.8 and 0.5 mg/kg, respectively, corresponding to plasma levels of 270.8 and 9.2 ng/mL, respectively. On the basis of its superior pharmacologic and safety profile, 4 (mavatrep) was selected for clinical development for the treatment of pain.

  DOI：

  10.1021/acs.jmedchem.5b00132

文献信息

• Benzimidazole Modulators of VR1
  申请人：Player Mark R.

  公开号：US20070259936A1

  公开（公告）日：2007-11-08

  The invention is directed to compounds of Formula (I): to pharmaceutical compositions containing such compounds and to methods of treatment using them.

  这项发明涉及到式（I）的化合物，以及包含这些化合物的药物组合物，以及使用它们的治疗方法。
• BENZIMIDAZOLE MODULATORS OF VR1
  申请人：Player Mark R.

  公开号：US20110190344A1

  公开（公告）日：2011-08-04

  The invention is directed to compounds of Formula (I): to pharmaceutical compositions containing such compounds and to methods of treatment using them.

  该发明涉及公式（I）的化合物，涉及含有这些化合物的制药组合物以及使用它们的治疗方法。
• US7951829B2
  申请人：——

  公开号：US7951829B2

  公开（公告）日：2011-05-31
• [EN] BENZIMIDAZOLE MODULATORS OF VR1<br/>[FR] MODULATEURS DES RÉCEPTEURS VR1 DÉRIVÉS DU BENZIMIDAZOLE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2007130780A2

  公开（公告）日：2007-11-15

  [EN] The invention is directed to compounds of Formula (I): to pharmaceutical compositions containing such compounds and to methods of treatment using them.
  [FR] L'invention concerne des composés de formule (I) :, des compositions pharmaceutiques contenant de tels composés et des procédés de traitement utilisant ceux-ci.