6-acetamido-3-(4-methoxyphenyl)-2H-indeno[1,2-c]pyrazol-4-one | 478162-02-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 6-acetamido-3-(4-methoxyphenyl)-2H-indeno[1,2-c]pyrazol-4-one
• 英文别名: Indenopyrazole 3e；N-[3-(4-methoxyphenyl)-4-oxo-1H-indeno[1,2-c]pyrazol-6-yl]acetamide
• CAS: 478162-02-6
• 化学式: C₁₉H₁₅N₃O₃
• 分子量: 333.346
• InChiKey: CKGMKJDEOUWUOO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  84.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-acetamido-3-(4-methoxyphenyl)-2H-indeno[1,2-c]pyrazol-4-one 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 Indenopyrazole 3f
  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-乙酰基氨基邻苯二甲酸二甲酯 在 sodium hydride 、 对甲苯磺酸 、 一水合肼 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.33h， 生成 6-acetamido-3-(4-methoxyphenyl)-2H-indeno[1,2-c]pyrazol-4-one
  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+