3-(1-dimethylaminoethylidene)-5-(oxazol-5-yl)-1,3-dihydroindol-2-one

• 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: 3-(1-dimethylaminoethylidene)-5-(oxazol-5-yl)-1,3-dihydroindol-2-one
• 英文别名: 3-[1-(dimethylamino)ethylidene]-5-(1,3-oxazol-5-yl)-1H-indol-2-one
• 化学式: C₁₅H₁₅N₃O₂
• 分子量: 269.303
• InChiKey: UZKXAIDVCVMKBS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  58.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  磺胺 、 3-(1-dimethylaminoethylidene)-5-(oxazol-5-yl)-1,3-dihydroindol-2-one 以 乙醇 为溶剂， 反应 18.0h， 生成 4-[1-(5-oxazol-5-yl-2-oxo-1,2-dihydro-indol-3-ylidene)ethylamino]benzenesulfonamide
  参考文献：
  名称：

  Oxindole-Based Inhibitors of Cyclin-Dependent Kinase 2 (CDK2):  Design, Synthesis, Enzymatic Activities, and X-ray Crystallographic Analysis

  摘要：

  Two closely related classes of oxindole-based compounds, 1H-indole-2,3-dione 3-phenylhydrazones and 3-(anilinomethylene)-1,3-dihydro-2H-indol-2-ones, were shown to potently inhibit cyclin-dependent kinase 2 (CDK2). The initial lead compound was prepared as a homologue of the 3-benzylidene-1,3-dihydro-2H-indol-2-one class of kinase inhibitor. Crystallographic analysis of the lead compound bound to CDK2 provided the basis for analogue design. A semiautomated method of ligand docking was used to select compounds for synthesis, and a number of compounds with low nanomolar inhibitory activity versus CDK2 were identified. Enzyme binding determinants for several analogues were evaluated by X-ray crystallography. Compounds in this series inhibited CDK2 with a potency similar to 10-fold greater than that for CDK1. Members of this class of inhibitor cause an arrest of the cell cycle and have shown potential utility in the prevention of chemotherapy-induced alopecia.

  DOI：

  10.1021/jm010117d
• 作为产物：
  描述：

  1,1-二甲氧基-N,N-二甲基乙胺 、 5-(oxazol-5-yl)-1,3-dihydroindol-2-one 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 3-(1-dimethylaminoethylidene)-5-(oxazol-5-yl)-1,3-dihydroindol-2-one
  参考文献：
  名称：

  Oxindole-Based Inhibitors of Cyclin-Dependent Kinase 2 (CDK2):  Design, Synthesis, Enzymatic Activities, and X-ray Crystallographic Analysis

  摘要：

  Two closely related classes of oxindole-based compounds, 1H-indole-2,3-dione 3-phenylhydrazones and 3-(anilinomethylene)-1,3-dihydro-2H-indol-2-ones, were shown to potently inhibit cyclin-dependent kinase 2 (CDK2). The initial lead compound was prepared as a homologue of the 3-benzylidene-1,3-dihydro-2H-indol-2-one class of kinase inhibitor. Crystallographic analysis of the lead compound bound to CDK2 provided the basis for analogue design. A semiautomated method of ligand docking was used to select compounds for synthesis, and a number of compounds with low nanomolar inhibitory activity versus CDK2 were identified. Enzyme binding determinants for several analogues were evaluated by X-ray crystallography. Compounds in this series inhibited CDK2 with a potency similar to 10-fold greater than that for CDK1. Members of this class of inhibitor cause an arrest of the cell cycle and have shown potential utility in the prevention of chemotherapy-induced alopecia.

  DOI：

  10.1021/jm010117d

文献信息

• Oxindole-Based Inhibitors of Cyclin-Dependent Kinase 2 (CDK2):  Design, Synthesis, Enzymatic Activities, and X-ray Crystallographic Analysis
  作者：H. Neal Bramson、John Corona、Stephen T. Davis、Scott H. Dickerson、Mark Edelstein、Stephen V. Frye、Robert T. Gampe、Phil A. Harris、Anne Hassell、William D. Holmes、Robert N. Hunter、Karen E. Lackey、Brett Lovejoy、Michael J. Luzzio、Val Montana、Warren J. Rocque、David Rusnak、Lisa Shewchuk、James M. Veal、Duncan H. Walker、Lee F. Kuyper

  DOI：10.1021/jm010117d

  日期：2001.12.1

  Two closely related classes of oxindole-based compounds, 1H-indole-2,3-dione 3-phenylhydrazones and 3-(anilinomethylene)-1,3-dihydro-2H-indol-2-ones, were shown to potently inhibit cyclin-dependent kinase 2 (CDK2). The initial lead compound was prepared as a homologue of the 3-benzylidene-1,3-dihydro-2H-indol-2-one class of kinase inhibitor. Crystallographic analysis of the lead compound bound to CDK2 provided the basis for analogue design. A semiautomated method of ligand docking was used to select compounds for synthesis, and a number of compounds with low nanomolar inhibitory activity versus CDK2 were identified. Enzyme binding determinants for several analogues were evaluated by X-ray crystallography. Compounds in this series inhibited CDK2 with a potency similar to 10-fold greater than that for CDK1. Members of this class of inhibitor cause an arrest of the cell cycle and have shown potential utility in the prevention of chemotherapy-induced alopecia.