1-[2-(4-Methoxy-benzoyl)-1,3-dioxo-indan-4-yl]-3-morpholin-4-yl-urea | 485820-07-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-[2-(4-Methoxy-benzoyl)-1,3-dioxo-indan-4-yl]-3-morpholin-4-yl-urea
• CAS: 485820-07-3
• 化学式: C₂₂H₂₁N₃O₆
• 分子量: 423.425
• InChiKey: YPSWNARHMCMDCZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.94
• 重原子数：
  31.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  114.04
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  1-[2-(4-Methoxy-benzoyl)-1,3-dioxo-indan-4-yl]-3-morpholin-4-yl-urea 在 对甲苯磺酸 、 一水合肼 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 1-[3-(4-methoxy-phenyl)-4-oxo-2,4-dihydro-indeno[1,2-c]pyrazol-5-yl]-3-morpholin-4-yl-urea
  参考文献：
  名称：

  Synthesis and Evaluation of Indenopyrazoles as Cyclin-Dependent Kinase Inhibitors. 2. Probing the Indeno Ring Substituent Pattern

  摘要：

  We disclose a novel series of indenopyrazole-based cyclin-dependent kinase (CDK) inhibitors. Kinetic experiments confirmed our initial molecular modeling studies that the compounds are competitive with respect to adenosine 5'-triphosphate (ATP) and bind in the kinase ATP pocket. A unique combination of active pharmacophores led us to a series of semicarbazide-based. inhibitors that are highly potent against CDK2 and CDK4 while maintaining selectivity against other relevant serine/threonine kinases. These compounds were active against a transformed human colon cancer cell line (HCT116) while maintaining an acceptable margin of activity against a normal fibroblast cell line. The compounds were found to be highly protein bound in our cell-based assay with the exception of 11k, which maintained a reasonable level of activity in the presence of human plasma proteins.

  DOI：

  10.1021/jm020171+
• 作为产物：
  描述：

  4-乙酰氨基-2-(4-甲氧基苯甲酰基)-1,3-二酮 在 4-二甲氨基吡啶 、 sodium carbonate 作用下， 以 二甲基亚砜 、 丙酮 为溶剂， 反应 9.0h， 生成 1-[2-(4-Methoxy-benzoyl)-1,3-dioxo-indan-4-yl]-3-morpholin-4-yl-urea
  参考文献：
  名称：

  Synthesis and Evaluation of Indenopyrazoles as Cyclin-Dependent Kinase Inhibitors. 2. Probing the Indeno Ring Substituent Pattern

  摘要：

  We disclose a novel series of indenopyrazole-based cyclin-dependent kinase (CDK) inhibitors. Kinetic experiments confirmed our initial molecular modeling studies that the compounds are competitive with respect to adenosine 5'-triphosphate (ATP) and bind in the kinase ATP pocket. A unique combination of active pharmacophores led us to a series of semicarbazide-based. inhibitors that are highly potent against CDK2 and CDK4 while maintaining selectivity against other relevant serine/threonine kinases. These compounds were active against a transformed human colon cancer cell line (HCT116) while maintaining an acceptable margin of activity against a normal fibroblast cell line. The compounds were found to be highly protein bound in our cell-based assay with the exception of 11k, which maintained a reasonable level of activity in the presence of human plasma proteins.

  DOI：

  10.1021/jm020171+