5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-6-carbonitrile | 1613504-86-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并吡啶类
• 英文名称: 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-6-carbonitrile
• CAS: 1613504-86-1
• 化学式: C₁₃H₁₂BrN₃O
• 分子量: 306.162
• InChiKey: FORIIODSIJJIEL-UHFFFAOYSA-N

物化性质

• 沸点：
  484.8±45.0 °C(predicted)
• 密度：
  1.63±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.37
• 重原子数：
  18.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  50.84
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-6-carbonitrile 在 盐酸 、 四(三苯基膦)钯 、 caesium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 生成 5-(2-(trifluoromethyl)phenyl)-1H-indazole-6-carbonitrile
  参考文献：
  名称：

  Discovery, Optimization, and Biological Evaluation of 5-(2-(Trifluoromethyl)phenyl)indazoles as a Novel Class of Transient Receptor Potential A1 (TRPA1) Antagonists

  摘要：

  A high throughput screening campaign identified 5-(2-chlorophenyl)indazole compound 4 as an antagonist of the transient receptor potential A1 (TRPA1) ion channel with IC50 = 1.23 μM. Hit to lead medicinal chemistry optimization established the SAR around the indazole ring system, demonstrating that a trifluoromethyl group at the 2-position of the phenyl ring in combination with various substituents at the 6-position of the indazole ring greatly contributed to improvements in vitro activity. Further lead optimization resulted in the identification of compound 31, a potent and selective antagonist of TRPA1 in vitro (IC50 = 0.015 μM), which has moderate oral bioavailability in rodents and demonstrates robust activity in vivo in several rodent models of inflammatory pain.

  DOI：

  10.1021/jm401986p
• 作为产物：
  描述：

  3-氨基-4-甲基苯甲腈 在 N-溴代丁二酰亚胺(NBS) 、 亚硝酸特丁酯 、 三氟化硼乙醚 、 对甲苯磺酸 作用下， 以 二氯甲烷 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 生成 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-6-carbonitrile
  参考文献：
  名称：

  Discovery, Optimization, and Biological Evaluation of 5-(2-(Trifluoromethyl)phenyl)indazoles as a Novel Class of Transient Receptor Potential A1 (TRPA1) Antagonists

  摘要：

  A high throughput screening campaign identified 5-(2-chlorophenyl)indazole compound 4 as an antagonist of the transient receptor potential A1 (TRPA1) ion channel with IC50 = 1.23 μM. Hit to lead medicinal chemistry optimization established the SAR around the indazole ring system, demonstrating that a trifluoromethyl group at the 2-position of the phenyl ring in combination with various substituents at the 6-position of the indazole ring greatly contributed to improvements in vitro activity. Further lead optimization resulted in the identification of compound 31, a potent and selective antagonist of TRPA1 in vitro (IC50 = 0.015 μM), which has moderate oral bioavailability in rodents and demonstrates robust activity in vivo in several rodent models of inflammatory pain.

  DOI：

  10.1021/jm401986p