N-(3-nitro-2',5-bis(trifluoromethyl)-[1,1'-biphenyl]-4-yl)-1,8-dioxa-2-azaspiro[4.5]dec-2-ene-3-carboxamide | 1276127-39-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(3-nitro-2',5-bis(trifluoromethyl)-[1,1'-biphenyl]-4-yl)-1,8-dioxa-2-azaspiro[4.5]dec-2-ene-3-carboxamide
• CAS: 1276127-39-9
• 化学式: C₂₂H₁₇F₆N₃O₅
• 分子量: 517.384
• InChiKey: IEVGCDCFHVTZLX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.56
• 重原子数：
  36.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  103.06
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  N-(3-nitro-2',5-bis(trifluoromethyl)-[1,1'-biphenyl]-4-yl)-1,8-dioxa-2-azaspiro[4.5]dec-2-ene-3-carboxamide 在 盐酸 、 铁粉 、 溶剂黄146 作用下， 以 甲醇 、 乙醇 、 异丙醇 为溶剂， 反应 4.5h， 生成 3-[7-trifluoromethyl-5-(2-trifluoromethylphenyl)-1H-benzimidazol-2-yl]-1,8-dioxa-2-azaspiro[4.5]dec-2-ene hydrochloride
  参考文献：
  名称：

  Design and Optimization of Benzimidazole-Containing Transient Receptor Potential Melastatin 8 (TRPM8) Antagonists

  摘要：

  Transient receptor potential melastatin 8 (TRPM8) is a nonselective cation channel that is thermo-responsive to cool to cold temperatures (8-28 degrees C) and also may be activated by chemical agonists such as menthol and Antagonism of TRPM8 activation is currently under investigation for the treatment of painful conditions related to cold, such as cold allodynia and cold hyperalgesia The design, synthesis, and optimization of a class of selective TRPM8 antagonists based on a benzimidazole scaffold is described, leading to the identification of compounds that exhibited potent antagonism of TRPM8 in cell-based functional assays for human, rat, and canine TRPM8 channels Numerous compounds in the series demonstrated excellent in vivo activity in the TRPM8-selective "wet-dog shakes" (WDS) pharmacodynamic model and in the rat chronic constriction injury (CCI)-induced model of neuropathic pain Taken together the present results suggest that the in vivo antagonism of TRPM8 constitutes a viable new strategy for treating a variety of disorders associated with cold hypersensitivity, including certain types of neuropathic pain

  DOI：

  10.1021/jm101075v
• 作为产物：
  描述：

  2-(三氟甲基)苯硼酸 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 sodium hydride 、 sodium carbonate 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 水 、 mineral oil 为溶剂， 反应 34.5h， 生成 N-(3-nitro-2',5-bis(trifluoromethyl)-[1,1'-biphenyl]-4-yl)-1,8-dioxa-2-azaspiro[4.5]dec-2-ene-3-carboxamide
  参考文献：
  名称：

  Design and Optimization of Benzimidazole-Containing Transient Receptor Potential Melastatin 8 (TRPM8) Antagonists

  摘要：

  Transient receptor potential melastatin 8 (TRPM8) is a nonselective cation channel that is thermo-responsive to cool to cold temperatures (8-28 degrees C) and also may be activated by chemical agonists such as menthol and Antagonism of TRPM8 activation is currently under investigation for the treatment of painful conditions related to cold, such as cold allodynia and cold hyperalgesia The design, synthesis, and optimization of a class of selective TRPM8 antagonists based on a benzimidazole scaffold is described, leading to the identification of compounds that exhibited potent antagonism of TRPM8 in cell-based functional assays for human, rat, and canine TRPM8 channels Numerous compounds in the series demonstrated excellent in vivo activity in the TRPM8-selective "wet-dog shakes" (WDS) pharmacodynamic model and in the rat chronic constriction injury (CCI)-induced model of neuropathic pain Taken together the present results suggest that the in vivo antagonism of TRPM8 constitutes a viable new strategy for treating a variety of disorders associated with cold hypersensitivity, including certain types of neuropathic pain

  DOI：

  10.1021/jm101075v