| 1350725-40-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• CAS: 1350725-40-4
• 化学式: C₉H₄ClF₃N₂O
• 分子量: 248.592
• InChiKey: SSNHLYFNSVTNTJ-UHFFFAOYSA-N

物化性质

• 密度：
  1.604±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.96
• 重原子数：
  16.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  45.75
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  在 四(三苯基膦)钯 、 potassium carbonate 、 caesium carbonate 、 三乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 sodium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 14.0h， 生成 C₂₀H₁₉N₅O₂
  参考文献：
  名称：

  Discovery and optimization of indole and 7-azaindoles as Rho kinase (ROCK) inhibitors (Part-II)

  摘要：

  Therapeutic interventions with Rho kinase (ROCK) inhibitors may effectively treat several disorders such as hypertension, stroke, cancer, and glaucoma. Herein we disclose the optimization and biological evaluation of potent novel ROCK inhibitors based on substituted indole and 7-azaindole core scaffolds. Substitutions on the indole C3 position and on the indole NH and/or amide NH positions all yielded potent and selective ROCK inhibitors (25, 42, and 50). Improvement of aqueous solubility and tailoring of in vitro and in vivo DMPK properties could be achieved through these substitutions. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.084
• 作为产物：
  描述：

  7-氮杂吲哚 在 甲醇 、 间氯过氧苯甲酸 、 六甲基二硅氮烷 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 27.08h， 生成
  参考文献：
  名称：

  Discovery and optimization of indoles and 7-azaindoles as Rho kinase (ROCK) inhibitors (part-I)

  摘要：

  Rho kinase (ROCK) inhibitors are potential therapeutic agents to treat disorders such as hypertension, multiple sclerosis, cancers, and glaucoma. Here, we disclose the synthesis, optimization, biological evaluation of potent indole and 7-azaindole based ROCK inhibitors that have high potency on ROCK (IC50 = 1 nM) with 740-fold selectivity over PKA (47). Moreover, 47 showed very good DMPK properties making it a good candidate for further development. Finally, docking studies with a homology model of ROCK-II were performed to rationalize the binding mode of these compounds and showed the compounds bound in both orientations to take advantage to H-bonds with Lys-121 of ROCK-II. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.083