3-(1-benzyl-1H-indazol-3-yloxy)-propylamine | 36504-74-2

• 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: 3-(1-benzyl-1H-indazol-3-yloxy)-propylamine
• 英文别名: 1-Benzyl-3-γ-aminopropyl-1H-indazol；1-Benzyl-3-(3-aminopropoxy)-1H-indazol；3-(1-benzylindazol-3-yl)oxypropan-1-amine
• CAS: 36504-74-2
• 化学式: C₁₇H₁₉N₃O
• 分子量: 281.357
• InChiKey: KFNKPAYXEHELQT-UHFFFAOYSA-N

物化性质

• 沸点：
  483.3±35.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  53.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-苄基-3-羟基-1H-吲唑 在 sodium hydride 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.25h， 生成 3-(1-benzyl-1H-indazol-3-yloxy)-propylamine
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Novel Pyrazoles and Indazoles as Activators of the Nitric Oxide Receptor, Soluble Guanylate Cyclase

  摘要：

  Database searching and compound screening identified 1-benzyl-3-(3-dimethylaminopropyloxy)-indazole (benzydamine, 3) as a potent activator of the nitric oxide receptor, soluble guanylate cyclase. A comprehensive structure-activity relationship study surrounding 3 clearly showed that the indazole C-3 dimethylaminopropyloxy substituent was critical for enzyme activity. However replacement of the indazole ring of 3 by appropriately substituted pyrazoles maintained enzyme activity. Compounds were evaluated for inhibition of platelet aggregation and showed a general lipophilicity requirement. Aryl-substituted pyrazoles 32, 34, and 43 demonstrated potent activation of soluble guanylate cyclase and potent inhibition of platelet aggregation. Pharmacokinetic studies in rats showed that compound 32 exhibits modest oral bioavailability (12%). Furthermore 32 has an excellent selectivity profile notably showing no significant inhibition of phosphodiesterases or nitric oxide synthases.

  DOI：

  10.1021/jm001034k

文献信息

• Synthesis and Biological Evaluation of Novel Pyrazoles and Indazoles as Activators of the Nitric Oxide Receptor, Soluble Guanylate Cyclase
  作者：David L. Selwood、David G. Brummell、Joanna Budworth、Guillaume E. Burtin、Richard O. Campbell、Surinder S. Chana、Ian G. Charles、Patricia A. Fernandez、Robert C. Glen、Maria C. Goggin、Adrian J. Hobbs、Marcel R. Kling、Qian Liu、David J. Madge、Sylvie Meillerais、Kenneth L. Powell、Karen Reynolds、Graham D. Spacey、Jeremy N. Stables、Mark A. Tatlock、Kerry A. Wheeler、Grant Wishart、Chi-Kit Woo

  DOI：10.1021/jm001034k

  日期：2001.1.1

  Database searching and compound screening identified 1-benzyl-3-(3-dimethylaminopropyloxy)-indazole (benzydamine, 3) as a potent activator of the nitric oxide receptor, soluble guanylate cyclase. A comprehensive structure-activity relationship study surrounding 3 clearly showed that the indazole C-3 dimethylaminopropyloxy substituent was critical for enzyme activity. However replacement of the indazole ring of 3 by appropriately substituted pyrazoles maintained enzyme activity. Compounds were evaluated for inhibition of platelet aggregation and showed a general lipophilicity requirement. Aryl-substituted pyrazoles 32, 34, and 43 demonstrated potent activation of soluble guanylate cyclase and potent inhibition of platelet aggregation. Pharmacokinetic studies in rats showed that compound 32 exhibits modest oral bioavailability (12%). Furthermore 32 has an excellent selectivity profile notably showing no significant inhibition of phosphodiesterases or nitric oxide synthases.