5-(4-carbamoylbenzylaminocarbonyl)-1,3-dihydropyrrolo-[3,4-c]carbazole-1,3(2H,6H)-dione | 1225189-69-4

• 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: 5-(4-carbamoylbenzylaminocarbonyl)-1,3-dihydropyrrolo-[3,4-c]carbazole-1,3(2H,6H)-dione
• 英文别名: N-[(4-carbamoylphenyl)methyl]-1,3-dioxo-6H-pyrrolo[3,4-c]carbazole-5-carboxamide
• CAS: 1225189-69-4
• 化学式: C₂₃H₁₆N₄O₄
• 分子量: 412.404
• InChiKey: RPSVAJWULGQWLL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  134
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-(4-cyanobenzylaminocarbonyl)-1,3-dihydropyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione 在 双氧水 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 22.0h， 以48%的产率得到5-(4-carbamoylbenzylaminocarbonyl)-1,3-dihydropyrrolo-[3,4-c]carbazole-1,3(2H,6H)-dione
  参考文献：
  名称：

  Synthesis and evaluation of 5-substituted 9-hydroxypyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones as check point 1 kinase inhibitors

  摘要：

  The structure-activity relationship (SAR) of 5-substituted pyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione derivatives 5 was investigated for their potential as Chk1 inhibitors for possible chemo- and radio-potentiators in anticancer chemotherapies. In silico virtual screening helped to optimize the substituent on the phenyl ring, and led to identification of the m-carbamoyl group among the 117 analogues tested. Further optimization studies focusing on the docking model of 15 in the active site of Chk1 revealed that 32b (IC50 = 2.8 nM) was a more potent inhibitor than UNC-01. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.09.042

文献信息

• Synthesis and evaluation of 5-substituted 9-hydroxypyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones as check point 1 kinase inhibitors
  作者：Yuki Sako、Satoshi Ichikawa、Akiko Osada、Akira Matsuda

  DOI：10.1016/j.bmc.2010.09.042

  日期：2010.11.15

  The structure-activity relationship (SAR) of 5-substituted pyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione derivatives 5 was investigated for their potential as Chk1 inhibitors for possible chemo- and radio-potentiators in anticancer chemotherapies. In silico virtual screening helped to optimize the substituent on the phenyl ring, and led to identification of the m-carbamoyl group among the 117 analogues tested. Further optimization studies focusing on the docking model of 15 in the active site of Chk1 revealed that 32b (IC50 = 2.8 nM) was a more potent inhibitor than UNC-01. (C) 2010 Elsevier Ltd. All rights reserved.