6-Bromo-2-[(E)-2-(4-chloro-phenyl)-vinyl]-1H-benzoimidazole

• 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: 6-Bromo-2-[(E)-2-(4-chloro-phenyl)-vinyl]-1H-benzoimidazole
• 化学式: C₁₅H₁₀BrClN₂
• 分子量: 333.615
• InChiKey: LBVNDCNXWZPTML-FPYGCLRLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.15
• 重原子数：
  19.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  28.68
• 氢给体数：
  1.0
• 氢受体数：
  1.0

反应信息

• 作为产物：
  描述：

  (E)-2-(4-chlorostyryl)-1H-benzo[d]imidazole 在 溴 作用下， 以 溶剂黄146 为溶剂， 反应 3.0h， 以57%的产率得到6-Bromo-2-[(E)-2-(4-chloro-phenyl)-vinyl]-1H-benzoimidazole
  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：——