5-[3-(2-aminoethylcarbamoyl)benzylaminocarboyl]-9-hydroxy-1,3-dihydropyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione hydrochloride | 1225190-10-2

• 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-[3-(2-aminoethylcarbamoyl)benzylaminocarboyl]-9-hydroxy-1,3-dihydropyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione hydrochloride
• 英文别名: N-[[3-(2-aminoethylcarbamoyl)phenyl]methyl]-9-hydroxy-1,3-dioxo-6H-pyrrolo[3,4-c]carbazole-5-carboxamide;hydrochloride
• CAS: 1225190-10-2
• 化学式: C₂₅H₂₁N₅O₅*ClH
• 分子量: 507.933
• InChiKey: KRUBKKNMNZBPCF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.95
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  166
• 氢给体数：
  7
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-[3-(2-aminoethylcarbamoyl)benzylaminocarboyl]-9-hydroxy-1,3-dihydropyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione hydrochloride 、 N,N′-二-Boc-硫脲 在 三乙胺 、 mercury dibromide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以54%的产率得到5-(3-[2-(di-tert-butoxycarbonylguanidino)ethylcarbamoyl]benzylaminocarboyl)-9-hydroxy-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
• 作为产物：
  描述：

  5-(3-[(2-tert-butoxycarbonylamino)ethylcarbamoyl]-benzylaminocarboyl)-9-hydroxy-1,3-dihydropyrrolo[3,4-c]-carbazole-1,3(2H,6H)-dione 在 盐酸 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 4.5h， 以86%的产率得到5-[3-(2-aminoethylcarbamoyl)benzylaminocarboyl]-9-hydroxy-1,3-dihydropyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione hydrochloride
  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