N-[(1S)-1-(3-methoxyphenyl)ethyl]-6-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide | 1350353-85-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: N-[(1S)-1-(3-methoxyphenyl)ethyl]-6-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide
• CAS: 1350353-85-3
• 化学式: C₂₀H₁₉N₅O₂
• 分子量: 361.403
• InChiKey: JAWPAUHQCGKVGI-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  95.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氨基-6-氯吡啶 在 三乙烯二胺 、 盐酸 、 四(三苯基膦)钯 、 叔丁基锂 、 palladium diacetate 、 potassium carbonate 、 三乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 35.0h， 生成 N-[(1S)-1-(3-methoxyphenyl)ethyl]-6-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide
  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

文献信息

• Discovery and optimization of indoles and 7-azaindoles as Rho kinase (ROCK) inhibitors (part-I)
  作者：Sarwat Chowdhury、E. Hampton Sessions、Jennifer R. Pocas、Wayne Grant、Thomas Schröter、Li Lin、Claudia Ruiz、Michael D. Cameron、Stephan Schürer、Philip LoGrasso、Thomas D. Bannister、Yangbo Feng

  DOI：10.1016/j.bmcl.2011.09.083

  日期：2011.12

  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.