(R)-N-(1-(3-methoxyphenyl)ethyl)-6-(1H-pyrazol-4-yl)-1H-indole-3-carboxamide | 1296199-38-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (R)-N-(1-(3-methoxyphenyl)ethyl)-6-(1H-pyrazol-4-yl)-1H-indole-3-carboxamide
• 英文别名: N-[(1R)-1-(3-methoxyphenyl)ethyl]-6-(1H-pyrazol-4-yl)-1H-indole-3-carboxamide
• CAS: 1296199-38-6
• 化学式: C₂₁H₂₀N₄O₂
• 分子量: 360.415
• InChiKey: CMZGQSDEDHCVNT-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  82.8
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-(6-bromo-1H-indol-3-yl)-2,2,2-trifluoroethanone 在 trans-bis(triphenylphosphine)palladium dichloride 、 水 、 sodium 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 四氢呋喃 、 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 (R)-N-(1-(3-methoxyphenyl)ethyl)-6-(1H-pyrazol-4-yl)-1H-indole-3-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

• [EN] BICYCLIC HETEROARYLS AS KINASE INHIBITORS<br/>[FR] HÉTÉROARYLES BICYCLIQUES FORMANT INHIBITEURS DE LA KINASE
  申请人：FENG YANGBO

  公开号：WO2011050245A1

  公开（公告）日：2011-04-28

  The invention is directed to heteroaryl compounds useful as inhibitors of various kinase enzymes. In various embodiments, the invention provides a heteroaryl compound having inhibitory bioactivity with respect to a Rho kinase, an AKT kinase, a p70S6K kinase, a LIM kinase, an IKK kinase, a Flt kinase, an Aurora kinase, or a Src kinase, or any combination thereof. Compounds of the invention include bicyclic heteroaryl compounds of formula (I), which can contain a bridging nitrogen atom at a ring junction. The invention further provides methods of synthesis of compounds of the invention, pharmaceutical compositions, pharmaceutical combinations, and methods of treatment of malconditions using compounds of the invention.

  该发明涉及对各种激酶酶的抑制剂作为杂环芳基化合物的用途。在各种实施形式中，该发明提供了一种具有抑制生物活性的杂环芳基化合物，该生物活性与Rho激酶、AKT激酶、p70S6K激酶、LIM激酶、IKK激酶、Flt激酶、Aurora激酶或Src激酶或其任意组合相关。该发明的化合物包括具有式(I)的双环杂环芳基化合物，该化合物在环的连接处可以含有一个桥接氮原子。该发明还提供了合成该发明化合物的方法、药物组合物、药物组合以及使用该发明化合物治疗病症的方法。
• 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.