(E)-5-bromo-2-[2-(4-tolyl)vinyl]-1H-benzo[d]imidazole

• 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-tolyl)vinyl]-1H-benzo[d]imidazole
• 英文别名: 5-Bromo-2-(2-p-tolyl-vinyl)-1H-benzimidazole；6-bromo-2-[(E)-2-(4-methylphenyl)ethenyl]-1H-benzimidazole
• 化学式: C₁₆H₁₃BrN₂
• 分子量: 313.197
• InChiKey: HBFUZKJGDYSNIQ-RMKNXTFCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 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：

  2-甲磺酰氨基苯硼酸 、 (E)-5-bromo-2-[2-(4-tolyl)vinyl]-1H-benzo[d]imidazole 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 caesium carbonate 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 18.0h， 生成 (trans)-N-{2-[2-(2-p-tolylvinyl)-1H-benzoimidazol-5-yl]phenyl}methanesulfonamide
  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：

  2-[(E)-2-(4-methylphenyl)ethenyl]-1H-benzimidazole 在 溴 作用下， 以 溶剂黄146 为溶剂， 反应 3.0h， 以55%的产率得到(E)-5-bromo-2-[2-(4-tolyl)vinyl]-1H-benzo[d]imidazole
  参考文献：
  名称：

  Dubey; Kumar, Ramesh; Cameron, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1999, vol. 38, # 8, p. 914 - 919

  摘要：

  DOI：

文献信息

• Benzo[<i>d</i>]imidazole Transient Receptor Potential Vanilloid 1 Antagonists for the Treatment of Pain: Discovery of <i>trans</i>-2-(2-{2-[2-(4-Trifluoromethyl-phenyl)-vinyl]-1<i>H</i>-benzimidazol-5-yl}-phenyl)-propan-2-ol (Mavatrep)
  作者：William H. Parsons、Raul R. Calvo、Wing Cheung、Yu-Kai Lee、Sharmila Patel、Jian Liu、Mark A. Youngman、Scott L. Dax、Dennis Stone、Ning Qin、Tasha Hutchinson、Mary Lou Lubin、Sui-Po Zhang、Michael Finley、Yi Liu、Michael R. Brandt、Christopher M. Flores、Mark R. Player

  DOI：10.1021/acs.jmedchem.5b00132

  日期：2015.5.14

  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.
• Dubey; Kumar, Ramesh; Cameron, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1999, vol. 38, # 8, p. 914 - 919
  作者：Dubey、Kumar, Ramesh、Cameron、Grossert、Hooper

  DOI：——

  日期：——