11-benzoyl-10-chloro-7,9-difluoro-6-imino-2,3,4,6-tetrahydro-1H-pyrimido[1,2-b]isoquinoline-8-carbonitrile | 1192010-61-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 11-benzoyl-10-chloro-7,9-difluoro-6-imino-2,3,4,6-tetrahydro-1H-pyrimido[1,2-b]isoquinoline-8-carbonitrile
• 英文别名: 6-imino-11-benzoyl-10-chloro-7,9-difluoro-2,3,4,6-tetrahydro-1H-pyrimido[1,2-b]isoquinoline-8-carbonitrile；11-Benzoyl-10-chloro-7,9-difluoro-6-imino-1,2,3,4-tetrahydropyrimido[1,2-b]isoquinoline-8-carbonitrile；11-benzoyl-10-chloro-7,9-difluoro-6-imino-1,2,3,4-tetrahydropyrimido[1,2-b]isoquinoline-8-carbonitrile
• CAS: 1192010-61-9
• 化学式: C₂₀H₁₃ClF₂N₄O
• 分子量: 398.799
• InChiKey: BAKRSVYPESSVNS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  80
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  11-benzoyl-10-chloro-7,9-difluoro-6-imino-2,3,4,6-tetrahydro-1H-pyrimido[1,2-b]isoquinoline-8-carbonitrile 在 盐酸 、 水 、 sodium carbonate 作用下， 以 乙醇 、 水 为溶剂， 反应 24.0h， 以79%的产率得到11-benzoyl-7,9-difluoro-10-chloro-8-cyano-6-oxo-2,3,4,6-tetrahydro-1H-pyrimidino[1,2-b]isoquinoline
  参考文献：
  名称：

  Facile Route to 1,3-Diazaheterocycle-Fused [1,2b]Isoquinolin-1(2H)-one Derivatives via Substitution-Cyclization Reactions

  摘要：

  The substitution-cyclization reaction of heterocyclic ketene aminals with polyhalo isophthalonitrile in the presence of t-BuOK to form 1,3-diazaheterocycle fused [1,2-b]isoquinolin-1(2H)-imines, followed by hydrolysis with 1N HCl, provides a concise and efficient route for the synthesis of highly functional polyhalo 1,3-diazaheterocycle fused [1,2-b]isoquinolin-1(2H)-ones.

  DOI：

  10.1021/cc900121c
• 作为产物：
  描述：

  在 potassium tert-butylate 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.5h， 生成 11-benzoyl-10-chloro-7,9-difluoro-6-imino-2,3,4,6-tetrahydro-1H-pyrimido[1,2-b]isoquinoline-8-carbonitrile
  参考文献：
  名称：

  Facile Route to 1,3-Diazaheterocycle-Fused [1,2b]Isoquinolin-1(2H)-one Derivatives via Substitution-Cyclization Reactions

  摘要：

  The substitution-cyclization reaction of heterocyclic ketene aminals with polyhalo isophthalonitrile in the presence of t-BuOK to form 1,3-diazaheterocycle fused [1,2-b]isoquinolin-1(2H)-imines, followed by hydrolysis with 1N HCl, provides a concise and efficient route for the synthesis of highly functional polyhalo 1,3-diazaheterocycle fused [1,2-b]isoquinolin-1(2H)-ones.

  DOI：

  10.1021/cc900121c

文献信息

• An Isoquinolin‐1(2 <i>H</i> )‐Imine Derivative Induces Cell Death via Generation of Reactive Oxygen Species and Activation of JNK in Human A549 Cancer Cells
  作者：Jing Liu、Tongyang Liu、Hanchuan Mou、Shuting Jia、Chao Huang、Shengjiao Yan、Jun Lin、Ying Luo、Jihong Zhang

  DOI：10.1002/jcb.26093

  日期：2017.12

  nitrile (HC6h) is a novel polyhalo 1,3-diazaheterocycle fused isoquinolin-1(2H)-imines derivative, which displays good anticancer activity and low toxicity in vivo. However, the underlying anticancer mechanisms have not previously been identified. The proliferation of A549 was assessed by MTT assay. The reactive oxygen species (ROS) level was assessed in A549 with a H2 DCFDA probe. Mitochondrial membrane

  化合物 11-benzoyl-10-chloro-7,9-difluoro-6-imino-2,3,4,6-tetrahydro-1H-pyrimido[1,2-b]isoquinoline-8-carbonitrile (HC6h)多卤 1,3-二氮杂杂环稠合异喹啉-1(2H)-亚胺衍生物，在体内表现出良好的抗癌活性和低毒性。然而，先前尚未确定潜在的抗癌机制。通过MTT测定评估A549的增殖。使用 H2 DCFDA 探针在 A549 中评估活性氧 (ROS) 水平。使用 JC-1 染色测量线粒体膜电位。通过膜联蛋白-V/PI 测定法测量细胞凋亡，通过吖啶橙染色和 GFP-LC3 荧光测定法测量自噬。自噬和凋亡蛋白的表达通过蛋白质印迹法测定。化合物 HC6h 增加了囊泡的积累，吖啶橙染色的细胞和 A549 细胞中的 LC3-II。bafilomycin A1 抑制化合物 HC6h 诱导的自噬增加了细胞凋亡。化合物
• Biological evaluation of polyhalo 1,3-diazaheterocycle fused isoquinolin-1(2H)-imine derivatives
  作者：Chao Huang、Sheng-Jiao Yan、Xiang-Hui Zeng、Xiao-Yang Dai、Yin Zhang、Chen Qing、Jun Lin

  DOI：10.1016/j.ejmech.2011.01.036

  日期：2011.4

  A series of polyhalo 1,3-diazaheterocycle fused isoquinolin-1(2H)-imines were evaluated in vitro against human tumour cell lines including A431, K562, HL60, HepG2 and Skov-3. As a result, some of the target compounds such as 5b, 5c, 5i, 5o, 6c, 6h and 7f showed stronger cytotoxicity against K562, H562 and Skov-3 cells in comparison with cisplatin, and the others displayed moderate cytotoxicity to A431 and HepG2. Biological investigations using the representative compounds 5c, 6c and 6h were also performed in mice bearing S(180) and H(22) tumours. The results indicated that these three compounds inhibit S(180) and H22 growth. In addition, compounds 6c and 6h have very low acute toxicities. The preliminary analysis of structure-activity relationships is also discussed. (C) 2011 Elsevier Masson SAS. All rights reserved.