3-[(5-acetyl-1,4,6,7-tetrahydropyrrolo[3,2-c]pyridin-2-yl)methylidene]-5-methoxy-1H-indol-2-one | 1446219-68-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: 3-[(5-acetyl-1,4,6,7-tetrahydropyrrolo[3,2-c]pyridin-2-yl)methylidene]-5-methoxy-1H-indol-2-one
• CAS: 1446219-68-6
• 化学式: C₁₉H₁₉N₃O₃
• 分子量: 337.378
• InChiKey: XCJXNMGPLVXHMC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  74.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  Pyrrolo[3,2-c]pyridine-2-carboxaldehyde, 4,5,6,7-tetrahydro-5-benzyl- 在 哌啶 、 palladium on activated charcoal 、 甲酸铵 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 生成 3-[(5-acetyl-1,4,6,7-tetrahydropyrrolo[3,2-c]pyridin-2-yl)methylidene]-5-methoxy-1H-indol-2-one
  参考文献：
  名称：

  Discovery of novel indolinone-based, potent, selective and brain penetrant inhibitors of LRRK2

  摘要：

  Mutations in leucine-rich repeat kinase-2 (LRRK2) are the most common genetic cause of Parkinson's disease (PD). The most frequent kinase-enhancing mutation is the G2019S residing in the kinase activation domain. This opens up a promising therapeutic avenue for drug discovery targeting the kinase activity of LRRK2 in PD. Several LRRK2 inhibitors have been reported to date. Here, we report a selective, brain penetrant LRRK2 inhibitor and demonstrate by a competition pulldown assay in vivo target engagement in mice. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.05.054

文献信息

• Discovery of novel indolinone-based, potent, selective and brain penetrant inhibitors of LRRK2
  作者：Thomas Troxler、Paulette Greenidge、Kaspar Zimmermann、Sandrine Desrayaud、Peter Drückes、Tatjana Schweizer、Daniela Stauffer、Giorgio Rovelli、Derya R. Shimshek

  DOI：10.1016/j.bmcl.2013.05.054

  日期：2013.7

  Mutations in leucine-rich repeat kinase-2 (LRRK2) are the most common genetic cause of Parkinson's disease (PD). The most frequent kinase-enhancing mutation is the G2019S residing in the kinase activation domain. This opens up a promising therapeutic avenue for drug discovery targeting the kinase activity of LRRK2 in PD. Several LRRK2 inhibitors have been reported to date. Here, we report a selective, brain penetrant LRRK2 inhibitor and demonstrate by a competition pulldown assay in vivo target engagement in mice. (C) 2013 Elsevier Ltd. All rights reserved.