6-(p-Methoxybenzoyl)-5H-1-pyrindin-5,7(6H)-dion | 32207-46-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-(p-Methoxybenzoyl)-5H-1-pyrindin-5,7(6H)-dion
• 英文别名: 6-(4-methoxy-benzoyl)-[1]pyrindine-5,7-dione；6-(4-Methoxybenzoyl)cyclopenta[b]pyridine-5,7-dione
• CAS: 32207-46-8
• 化学式: C₁₆H₁₁NO₄
• 分子量: 281.268
• InChiKey: WHYRREMSLTUUEX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  73.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-(p-Methoxybenzoyl)-5H-1-pyrindin-5,7(6H)-dion 在 对甲苯磺酸 、 一水合肼 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 3-(4-Methoxy-phenyl)-2H-pyrazolo[4',3':4,5]cyclopenta[1,2-b]pyridin-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+
• 作为产物：
  描述：

  2,3-吡啶二甲酸二甲酯 、 对甲氧基苯乙酮 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.33h， 生成 6-(p-Methoxybenzoyl)-5H-1-pyrindin-5,7(6H)-dion
  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+

文献信息

• Synthesis and Evaluation of Indenopyrazoles as Cyclin-Dependent Kinase Inhibitors. 2. Probing the Indeno Ring Substituent Pattern
  作者：David A. Nugiel、Anup Vidwans、Anna-Marie Etzkorn、Karen A. Rossi、Pamela A. Benfield、Catherine R. Burton、Sarah Cox、Deborah Doleniak、Steven P. Seitz

  DOI：10.1021/jm020171+

  日期：2002.11.1

  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.