2-[4-(isopropylaminomethylene)phenyl]-1,4,5-trihydro-1H-[1,2]diazepine[4,5,6-cd]indole-3,6-dione

• 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: 2-[4-(isopropylaminomethylene)phenyl]-1,4,5-trihydro-1H-[1,2]diazepine[4,5,6-cd]indole-3,6-dione
• 英文别名: 2-[4-[(Propan-2-ylamino)methyl]phenyl]-3,10,11-triazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene-9,12-dione；2-[4-[(propan-2-ylamino)methyl]phenyl]-3,10,11-triazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraene-9,12-dione
• 化学式: C₂₀H₂₀N₄O₂
• 分子量: 348.404
• InChiKey: JKTIWQKWRMMZOA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  86
• 氢给体数：
  4
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-甲基-3-硝基苯甲酸 在 盐酸 、 sodium chlorite 、 sodium tetrahydroborate 、 N-溴代丁二酰亚胺(NBS) 、 四(三苯基膦)钯 、 氯化亚砜 、 sodium dihydrogen phosphate 、 palladium 10% on activated carbon 、 氢气 、 sodium carbonate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 3-甲基-1-丁烯 、 溶剂黄146 、 三乙胺 、 三氟乙酸 、 lithium chloride 、 三氯氧磷 、 三溴氧磷 、 过氧化苯甲酰 作用下， 以 四氢呋喃 、 甲醇 、 四氯化碳 、 乙醇 、 二氯甲烷 、 水 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 32.0h， 生成 2-[4-(isopropylaminomethylene)phenyl]-1,4,5-trihydro-1H-[1,2]diazepine[4,5,6-cd]indole-3,6-dione
  参考文献：
  名称：

  Identification of novel PARP-1 inhibitors: Drug design, synthesis and biological evaluation

  摘要：

  A series of AG014699 derivatives containing a novel scaffold of 2,3-dihydro-1H-[1,2] diazepino[4,5,6-cd] indole-1,4(6H)-dione were synthesized and evaluated for their inhibitory activities toward PARP-1 enzyme and two cell lines, MCF-7 cells and the BRCA1-deficient MDA-MB-436 cells. Our results demonstrated that of all AG014699 derivatives synthesized in this work, compounds 6 and 7 showed strong PARP-1 inhibitory activity (IC50 = 3.5 nM and 2.4 nM, respectively), only four and three times less potent than AG014699. Compound 6 also had significantly cell inhibitory activity against both MCF-7 cells (CC50 = 25.8 mu M) and the BRCA1-deficient MDA-MB-436 cells (CC50 = 5.4 mu M), nearly as good as AG014699, indicating that it can be a promising compound for further evaluation. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.08.060

文献信息

• Identification of novel PARP-1 inhibitors: Drug design, synthesis and biological evaluation
  作者：Zhouling Xie、Youli Zhou、Wei Zhao、He Jiao、Yu Chen、Yong Yang、Zhiyu Li

  DOI：10.1016/j.bmcl.2015.08.060

  日期：2015.10

  A series of AG014699 derivatives containing a novel scaffold of 2,3-dihydro-1H-[1,2] diazepino[4,5,6-cd] indole-1,4(6H)-dione were synthesized and evaluated for their inhibitory activities toward PARP-1 enzyme and two cell lines, MCF-7 cells and the BRCA1-deficient MDA-MB-436 cells. Our results demonstrated that of all AG014699 derivatives synthesized in this work, compounds 6 and 7 showed strong PARP-1 inhibitory activity (IC50 = 3.5 nM and 2.4 nM, respectively), only four and three times less potent than AG014699. Compound 6 also had significantly cell inhibitory activity against both MCF-7 cells (CC50 = 25.8 mu M) and the BRCA1-deficient MDA-MB-436 cells (CC50 = 5.4 mu M), nearly as good as AG014699, indicating that it can be a promising compound for further evaluation. (C) 2015 Elsevier Ltd. All rights reserved.