6-chloro-7-((4-methoxyphenyl)amino)isoquinoline-5,8-dione | 228574-27-4

• 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: 6-chloro-7-((4-methoxyphenyl)amino)isoquinoline-5,8-dione
• 英文别名: 6-chloro-7-(4-methoxyphenyl)amino-5,8-isoquinolinedione；6-Chloro-7-(4-methoxyanilino)isoquinoline-5,8-dione
• CAS: 228574-27-4
• 化学式: C₁₆H₁₁ClN₂O₃
• 分子量: 314.728
• InChiKey: DMRNLJKRCVCUHO-UHFFFAOYSA-N

物化性质

• 沸点：
  463.7±45.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  68.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-chloro-7-((4-methoxyphenyl)amino)isoquinoline-5,8-dione 在 sodium azide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 以68%的产率得到8-Methoxypyrido[3,4-b]phenazine-5,12-dione
  参考文献：
  名称：

  Synthesis of 6-chloroisoquinoline-5,8-diones and pyrido[3,4-b]phenazine-5,12-diones and evaluation of their cytotoxicity and DNA topoisomerase II inhibitory activity

  摘要：

  The substituted chloroisoquinolinediones and pyrido [3,4-b]phenazinediones were synthesized, and the cytotoxic activity and topoisomerase 11 inhibitory activity of the prepared compounds were evaluated. Chloroisoquinolinediones have been prepared by the reported method employing 6,7-dichloroisoquinoline-5,8-dione. The cyclization to pyrido [3,4-b]phenazinediones was achieved by adding the aqueous sodium azide solution to the dimethylformamide solution of corresponding chloroisoquinoline5,8-dione. The cytotoxicity of the synthesized compounds was evaluated by a SRB (Sulforhodamine B) assay against various cancer cell lines such as A549 (human lung cancer cell line), SNU-638 (human stomach cancer cell), Col2 (human colon cancer cell line), HT1080 (human fibrosarcoma cell line), and HL-60 (human leukemia cell line). Almost all the synthesized pyrido[3,4-b]phenazinediones showed greater cytotoxic potential than ellipticine (IC50 = 1.82-5.97 mu M). In general, the cytotoxicity of the pyrido[3,4-b]phenazinediones was higher than that of the corresponding chloroisoquinolinediones. The caco-2 cell permeability of selected compounds was 0.62 x 10(-6)-35.3 x 10(-6) cm/s. The difference in cytotoxic activity among tested compounds was correlated with the difference in permeability to some degree. To further investigate the cytotoxic mechanism, the topoisomerase II inhibitory activity of the synthesized compounds was estimated by a plasmid cleavage assay. Most of compounds showed the topoisomerase II inhibitory activity (28-100%) at 200 mu M. IC50 values for the most active compound 6a were 0.082 mu M. However, the compounds were inactive for DNA relaxation by topoisomerase I at 200 mu M. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.09.040
• 作为产物：
  描述：

  5-硝基异喹啉 在 palladium on activated charcoal sodium chlorate 、 sodium hydroxide 、 盐酸羟胺 、 氢气 作用下， 以 盐酸 、 甲醇 、 乙醇 为溶剂， 50.0~60.0 ℃ 、206.84 kPa 条件下， 反应 4.0h， 生成 6-chloro-7-((4-methoxyphenyl)amino)isoquinoline-5,8-dione
  参考文献：
  名称：

  Ryu, Chung-Kyu; Lee, In-Kyung; Jung, Sung-Hee, Medicinal Chemistry Research, 2000, vol. 10, # 1, p. 40 - 49

  摘要：

  DOI：

文献信息

• Synthesis and cytotoxic activities of 6-chloro-7-arylamino-5,8-isoquinolinediones
  作者：Chung-Kyu Ryu、In-Kyung Lee、Sung-Hee Jung、Chong-Ock Lee

  DOI：10.1016/s0960-894x(99)00152-3

  日期：1999.4

  6-Chloro-7-arylamino-5,8-isoquinolinediones were newly synthesized and evaluated for in vitro cytotoxic activities against five human solid tumor cell lines. Among them, 5b, 5c and 5d exhibited potent activities against the cell lines HCT-15 and SK-MEL-2. (C) 1999 Elsevier Science Ltd. All rights reserved.
• Fluorescent 1,4-Naphthoquinones To Visualize Diffuse and Dense-Core Amyloid Plaques in APP/PS1 Transgenic Mouse Brains
  作者：Naewoo Neo Shin、Hanna Jeon、Youngeun Jung、Seungyeop Baek、Sejin Lee、Hee Chan Yoo、Gi Hun Bae、Keunwan Park、Seung-Hoon Yang、Jung Min Han、Ikyon Kim、YoungSoo Kim

  DOI：10.1021/acschemneuro.9b00093

  日期：2019.6.19

  Recent clinical approvals of brain imaging radiotracers targeting amyloid-beta provided clinicians the tools to detect and confirm Alzheimer's disease pathology without autopsy or biopsy. While current imaging agents are effective in postsymptomatic Alzheimer's patients, there is much room for improvement in earlier diagnosis, hence prompting a need for new and improved amyloid imaging agents. Here we synthesized 41 novel 1,4-naphthoquinone derivatives and initially discovered 14 antiamyloidogenic compounds via in vitro amyloid-beta aggregation assay; however, qualitative analyses of these compounds produced conflicting results and required further investigation. Follow-up docking and biophysical studies revealed that four of these compounds penetrate the blood-brain barrier, directly bind to amyloid-beta aggregates, and enhance fluorescence properties upon interaction. These compounds specifically stain both diffuse and dense-core amyloid-beta plaques in brain sections of APP/PS1 double transgenic Alzheimer's mouse models. Our findings suggest 1,4-naphthoquinones as a new scaffold for amyloid-beta imaging agents for early stage Alzheimer's.
• Synthesis of 6-chloroisoquinoline-5,8-diones and pyrido[3,4-b]phenazine-5,12-diones and evaluation of their cytotoxicity and DNA topoisomerase II inhibitory activity
  作者：Jin Sung Kim、Hee-Kyung Rhee、Hyen Joo Park、In-Kyoung Lee、Sang Kook Lee、Myung-Eun Suh、Hwa Jeong Lee、Chung-Kyu Ryu、Hea-Young Park Choo

  DOI：10.1016/j.bmc.2006.09.040

  日期：2007.1.1

  The substituted chloroisoquinolinediones and pyrido [3,4-b]phenazinediones were synthesized, and the cytotoxic activity and topoisomerase 11 inhibitory activity of the prepared compounds were evaluated. Chloroisoquinolinediones have been prepared by the reported method employing 6,7-dichloroisoquinoline-5,8-dione. The cyclization to pyrido [3,4-b]phenazinediones was achieved by adding the aqueous sodium azide solution to the dimethylformamide solution of corresponding chloroisoquinoline5,8-dione. The cytotoxicity of the synthesized compounds was evaluated by a SRB (Sulforhodamine B) assay against various cancer cell lines such as A549 (human lung cancer cell line), SNU-638 (human stomach cancer cell), Col2 (human colon cancer cell line), HT1080 (human fibrosarcoma cell line), and HL-60 (human leukemia cell line). Almost all the synthesized pyrido[3,4-b]phenazinediones showed greater cytotoxic potential than ellipticine (IC50 = 1.82-5.97 mu M). In general, the cytotoxicity of the pyrido[3,4-b]phenazinediones was higher than that of the corresponding chloroisoquinolinediones. The caco-2 cell permeability of selected compounds was 0.62 x 10(-6)-35.3 x 10(-6) cm/s. The difference in cytotoxic activity among tested compounds was correlated with the difference in permeability to some degree. To further investigate the cytotoxic mechanism, the topoisomerase II inhibitory activity of the synthesized compounds was estimated by a plasmid cleavage assay. Most of compounds showed the topoisomerase II inhibitory activity (28-100%) at 200 mu M. IC50 values for the most active compound 6a were 0.082 mu M. However, the compounds were inactive for DNA relaxation by topoisomerase I at 200 mu M. (c) 2006 Elsevier Ltd. All rights reserved.
• Ryu, Chung-Kyu; Lee, In-Kyung; Jung, Sung-Hee, Medicinal Chemistry Research, 2000, vol. 10, # 1, p. 40 - 49
  作者：Ryu, Chung-Kyu、Lee, In-Kyung、Jung, Sung-Hee、Kang, Hye-Young、Lee, Chong-Ock

  DOI：——

  日期：——