(Z)-5-bromo-3-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-1,3-dihydro-indol-2-one | 1221433-66-4

• 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: (Z)-5-bromo-3-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-1,3-dihydro-indol-2-one
• 英文别名: (Z)-5-bromo-3-((3,5-dimethyl-1H-pyrrol-2-yl)methylene)indolin-2-one；(3Z)-5-bromo-3-[(3,5-dimethyl-1H-pyrrol-2-yl)methylidene]-1H-indol-2-one
• CAS: 1221433-66-4
• 化学式: C₁₅H₁₃BrN₂O
• 分子量: 317.185
• InChiKey: LPEYLYBUTNTMHW-GHXNOFRVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  44.9
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  3,5-二甲基-2-吡咯甲醛 、 5-溴氧化吲哚 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以50%的产率得到(Z)-5-bromo-3-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-1,3-dihydro-indol-2-one
  参考文献：
  名称：

  Synthesis, structure–activity relationship and crystallographic studies of 3-substituted indolin-2-one RET inhibitors

  摘要：

  The synthesis, structure-activity relationships (SAR) and structural data of a series of indolin-2-one inhibitors of RET tyrosine kinase are described. These compounds were designed to explore the available space around the indolinone scaffold within RET active site. Several substitutions at different positions were tested and biochemical data were used to draw a molecular model of steric and electrostatic interactions, which can be applied to design more potent and selective RET inhibitors. The crystal structures of RET kinase domain in complex with three inhibitors were solved. All three compounds bound in the ATP pocket and formed two hydrogen bonds with the kinase hinge region. Crystallographic analysis confirmed predictions from molecular modelling and helped re. ne SAR results. These data provide important information for the development of indolinone inhibitors for the treatment of RET-driven cancers. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.01.011

文献信息

• [EN] Novel Hybrid Compounds<br/>[FR] NOUVEAUX COMPOSÉS HYBRIDES
  申请人：UNIV GREENWICH

  公开号：WO2012025726A1

  公开（公告）日：2012-03-01

  This invention relates to novel hybrid compounds, of formula 1 wherein R1 to R7, L and Y are as defined herein, wherein Y denotes a histone deacetylase inhibiting moiety (such as a heterocycle, hydroxamic acid or diamine) and L denotes a linker group the invention also relates to processes for preparing them and their use as therapeutic agents and diagnostic agents.

  本发明涉及一种新型杂化化合物，其化学式为1，其中R1至R7、L和Y的定义如本文所述，其中Y表示组织脱乙酰酶抑制基团（如杂环、羟基酰胺或二胺），L表示连接基团，该发明还涉及其制备方法以及它们作为治疗剂和诊断剂的用途。
• USE OF NOVEL NEUROPROTECTIVE 3-SUBSTITUTED INDOLONE COMPOSITIONS
  申请人：D'Mello Santosh R.

  公开号：US20100298376A1

  公开（公告）日：2010-11-25

  The present invention provides compositions and methods of synthesizing optionally substituted 3-substituted indolin-2-ones and methods to employ the resultant compounds to protect against neurodegeneration including diseases such as Alzheimer's disease, Parkinson's disease, or Huntington's disease, and conditions such as ischemic stroke.
• Synthesis, structure–activity relationship and crystallographic studies of 3-substituted indolin-2-one RET inhibitors
  作者：Luca Mologni、Roberta Rostagno、Stefania Brussolo、Phillip P. Knowles、Svend Kjaer、Judith Murray-Rust、Enrico Rosso、Alfonso Zambon、Leonardo Scapozza、Neil Q. McDonald、Vittorio Lucchini、Carlo Gambacorti-Passerini

  DOI：10.1016/j.bmc.2010.01.011

  日期：2010.2

  The synthesis, structure-activity relationships (SAR) and structural data of a series of indolin-2-one inhibitors of RET tyrosine kinase are described. These compounds were designed to explore the available space around the indolinone scaffold within RET active site. Several substitutions at different positions were tested and biochemical data were used to draw a molecular model of steric and electrostatic interactions, which can be applied to design more potent and selective RET inhibitors. The crystal structures of RET kinase domain in complex with three inhibitors were solved. All three compounds bound in the ATP pocket and formed two hydrogen bonds with the kinase hinge region. Crystallographic analysis confirmed predictions from molecular modelling and helped re. ne SAR results. These data provide important information for the development of indolinone inhibitors for the treatment of RET-driven cancers. (C) 2010 Elsevier Ltd. All rights reserved.