1-(4-(Trifluoromethyl)phenyl)-2,3,4,5-tetrahydro-1H-benzo[c]-azepine | 1357261-77-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 1-(4-(Trifluoromethyl)phenyl)-2,3,4,5-tetrahydro-1H-benzo[c]-azepine
• CAS: 1357261-77-8
• 化学式: C₁₇H₁₆F₃N
• 分子量: 291.316
• InChiKey: SPHASELNXOXXTQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.33
• 重原子数：
  21.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  12.03
• 氢给体数：
  1.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  1-(4-(Trifluoromethyl)phenyl)-2,3,4,5-tetrahydro-1H-benzo[c]-azepine 、 异氰酸对氟苯基酯 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 N-(4-fluorophenyl)-1-(4-(trifluoromethyl)phenyl)-4,5-dihydro-1H-benzo[c]azepine-2(3H)-carboxamide
  参考文献：
  名称：

  Fused Piperidines as a Novel Class of Potent and Orally Available Transient Receptor Potential Melastatin Type 8 (TRPM8) Antagonists

  摘要：

  The transient receptor potential melastatin type 8 (TRPM8) is a nonselective cation channel primarily expressed in a subpopulation of sensory neurons that can be activated by a wide range of stimuli, including menthol, icilin, and cold temperatures (< 25 degrees C). Antagonism of TRPM8 is currently under investigation as a new approach for the treatment of pain. As a result of our screening efforts, we identified tetrahydrothienopyridine 4 as an inhibitor of icilin-induced calcium influx in CHO cells expressing recombinant rat TRPM8. Exploration of the structure-activity relationships of 4 led to the identification of a potent and orally bioavailable TRPM8 antagonist, tetrahydroisoquinoline 87. Compound 87 demonstrated target coverage in vivo after oral administration in a rat pharmacodynamic model measuring the prevention of icilin-induced wet-dog shakes (WDS).

  DOI：

  10.1021/jm2013634
• 作为产物：
  描述：

  N-(3-phenylpropyl)-4-(trifluoromethyl)benzamide 在 sodium tetrahydroborate 、 四磷十氧化物 、 磷酸 作用下， 以 甲醇 为溶剂， 反应 4.25h， 生成 1-(4-(Trifluoromethyl)phenyl)-2,3,4,5-tetrahydro-1H-benzo[c]-azepine
  参考文献：
  名称：

  Fused Piperidines as a Novel Class of Potent and Orally Available Transient Receptor Potential Melastatin Type 8 (TRPM8) Antagonists

  摘要：

  The transient receptor potential melastatin type 8 (TRPM8) is a nonselective cation channel primarily expressed in a subpopulation of sensory neurons that can be activated by a wide range of stimuli, including menthol, icilin, and cold temperatures (< 25 degrees C). Antagonism of TRPM8 is currently under investigation as a new approach for the treatment of pain. As a result of our screening efforts, we identified tetrahydrothienopyridine 4 as an inhibitor of icilin-induced calcium influx in CHO cells expressing recombinant rat TRPM8. Exploration of the structure-activity relationships of 4 led to the identification of a potent and orally bioavailable TRPM8 antagonist, tetrahydroisoquinoline 87. Compound 87 demonstrated target coverage in vivo after oral administration in a rat pharmacodynamic model measuring the prevention of icilin-induced wet-dog shakes (WDS).

  DOI：

  10.1021/jm2013634