ethyl 8,8-difluoro-1-oxa-2-azaspiro[4.5]dec-2-ene-3-carboxylate | 1259026-23-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑啉类
• 英文名称: ethyl 8,8-difluoro-1-oxa-2-azaspiro[4.5]dec-2-ene-3-carboxylate
• CAS: 1259026-23-7
• 化学式: C₁₁H₁₅F₂NO₃
• 分子量: 247.242
• InChiKey: IROBMAHMMXRMDW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  47.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 8,8-difluoro-1-oxa-2-azaspiro[4.5]dec-2-ene-3-carboxylate 在 草酰氯 、 lithium hydrochloride monohydrate 、 水 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 23.0h， 生成 8,8-difluoro-3-[5-(2-trifluoromethylphenyl)-1H-benzimidazol-2-yl]-1-oxa-2-azaspiro[4.5]dec-2-ene
  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：

  ethyl 2-chloro-2-(hydroxyamino)acetate 、 4,4-二氟环已酮 、 甲基三苯基溴化膦 在 sodium amide 、 N,N-二异丙基乙胺 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 84.0h， 以42%的产率得到ethyl 8,8-difluoro-1-oxa-2-azaspiro[4.5]dec-2-ene-3-carboxylate
  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

文献信息

• Design and Optimization of Benzimidazole-Containing Transient Receptor Potential Melastatin 8 (TRPM8) Antagonists
  作者：Daniel J. Parks、William H. Parsons、Raymond W. Colburn、Sanath K. Meegalla、Shelley K. Ballentine、Carl R. Illig、Ning Qin、Yi Liu、Tasha L. Hutchinson、Mary Lou Lubin、Dennis J. Stone、Judith F. Baker、Craig R. Schneider、Jianya Ma、Bruce P. Damiano、Christopher M. Flores、Mark R. Player

  DOI：10.1021/jm101075v

  日期：2011.1.13

  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