5-bromo-1H-indazole-6-carbonitrile | 1613504-80-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 5-bromo-1H-indazole-6-carbonitrile
• CAS: 1613504-80-5
• 化学式: C₈H₄BrN₃
• 分子量: 222.044
• InChiKey: HQQBOUVRHZXIGS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  52.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-bromo-1H-indazole-6-carbonitrile 在 盐酸 、 四(三苯基膦)钯 、 caesium carbonate 、 对甲苯磺酸 作用下， 以 1,4-二氧六环 、 甲醇 、 氯仿 、 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 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 5-bromo-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

文献信息

• P38 INHIBITORS AND METHODS OF USE THEREOF
  申请人：Munson Mark C.

  公开号：US20090149443A1

  公开（公告）日：2009-06-11

  Compounds of formula (I): in which A, B, X, Ar 1 , R 8 and R 4 have any of the meanings given in the specification, are inhibitors of p38 useful in the treatment and prevention of various disorders mediated by p38.

  化合物的公式(I)：其中A、B、X、Ar1、R8和R4具有规范中给出的任何含义，是p38的抑制剂，可用于治疗和预防由p38介导的各种疾病。
• US8026233B2
  申请人：——

  公开号：US8026233B2

  公开（公告）日：2011-09-27
• Discovery, Optimization, and Biological Evaluation of 5-(2-(Trifluoromethyl)phenyl)indazoles as a Novel Class of Transient Receptor Potential A1 (TRPA1) Antagonists
  作者：Lisa Rooney、Agnès Vidal、Anne-Marie D’Souza、Nick Devereux、Brian Masick、Valerie Boissel、Ryan West、Victoria Head、Rowan Stringer、Jianmin Lao、Matt J. Petrus、Ardem Patapoutian、Mark Nash、Natalie Stoakley、Moh Panesar、J. Martin Verkuyl、Andrew M. Schumacher、H. Michael Petrassi、David C. Tully

  DOI：10.1021/jm401986p

  日期：2014.6.26

  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.