6,7-二氯喹喔啉-5,8-二酮 | 102072-82-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 6,7-二氯喹喔啉-5,8-二酮
• 英文名称: 6,7-dichloroquinoxaline-5,8-dione
• 英文别名: 6,7-dichloro-5,8-quinoxalinedione
• CAS: 102072-82-2
• 化学式: C₈H₂Cl₂N₂O₂
• 分子量: 229.022
• InChiKey: SEYCJGXCYDOTGT-UHFFFAOYSA-N

物化性质

• 熔点：
  192-194 °C(Solv: chloroform (67-66-3))
• 沸点：
  341.5±42.0 °C(Predicted)
• 密度：
  1.72±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  59.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6,7-二氯喹喔啉-5,8-二酮 在 氢氧化钾 、 sodium tetrahydroborate 、 sodium azide 、 硫酸 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 7.5h， 生成 3-Ethyl-2-methylpyrazino[2,3-g]quinoxaline-5,10-dione
  参考文献：
  名称：

  Synthesis and Cytotoxicity of 2-Methyl-4,9-dihydro-1-substituted-1H-imidazo[4,5-g]quinoxaline-4,9-diones and 2,3-Disubstituted-5,10-pyrazino[2,3-g]quinoxalinediones

  摘要：

  Series of 2-methyl-4,9-dihydro-1H-imidazo[4,5-g]quinoxaline-4,9-diones and 5,10-pyrazino[2,3g]quinoxalinediones have been synthesized from 6,7-dichloro-5,8-quinoxalinedione for developing new anticancer drugs. Intercalation complex of 2-methyl-4,9-dihydro-1-methyl-1H-imidazo-[4,5-g]quinoxaline-4,9-dione with GC/GC base pairs by a computer graphics-aided method was parallel to the axis of the helix. The interaction energies of synthetic compounds were low. 2-Methyl-4,9-dihydro-1-(4-bromophenyl)-1H-imidazo[4,5-g]quinoxaline-4,9-dione, which has the lowest interaction energy of the test compounds, was identified as being more cytotoxic against human gastric adenocarcinoma cells (MKN 45) than adriamycin and cis-platin in vitro using the MTT assay. The IC50 value of this compound was 1.30 mu M, whereas those of adriamycin and cis-platin were 3.13 and 86.5 mu M, respectively. The cytotoxicity of 2,3-diethyl-5,10-pyrazino-[2,3-g]quinoxalinedione was comparable to that of adriamycin in the in vitro assay. However these compounds showed loss of activity on human lung adenocarcinoma cells (PC 14) and human colon adenocarcinoma cells (colon 205). These results suggest that 2-methyl-4,9-dihydrol-(4-bromophenyl)-1H-imidazo[4,5-g]quinoxaline-4,9-dione, with the lowest interaction energy, might be an excellent and selective antitumor agent against MKN 45.

  DOI：

  10.1021/jm970695n
• 作为产物：
  描述：

  对苯二甲醚 在 吡啶 、 氯化亚砜 、 ammonium cerium (IV) nitrate 、 硝酸 作用下， 以 氯仿 、 水 、 溶剂黄146 、 乙腈 为溶剂， 反应 24.12h， 生成 6,7-二氯喹喔啉-5,8-二酮
  参考文献：
  名称：

  Design, Synthesis, and Cytotoxicity of Indolizinoquinoxaline-5,12-dione Derivatives, Novel DNA Topoisomerase IB Inhibitors

  摘要：

  通过 6,7 二氯喹喔啉-5,8-二酮与活性亚甲基试剂和吡啶衍生物的杂环化反应，设计并合成了一系列新的吲哚喹喔啉-5,12-二酮衍生物。合成的化合物在微摩尔范围内对四种人类肿瘤细胞系（包括肺腺癌细胞、大细胞肺癌细胞、乳腺癌细胞和耐阿霉素的乳腺癌细胞）的生长具有显著的抑制活性。还研究了这些化合物对 DNA 拓扑异构酶 IB 活性的抑制作用。结果表明，吲哚嗪喹喔啉-5,12-二酮结构可能是抗癌药物设计中的潜在药源。

  DOI：

  10.1071/ch09580

文献信息

• Syntheses and antibacterial activity of soluble 9-bromo substituted indolizinoquinoline-5,12-dione derivatives
  作者：Hui Yang、Hao-Wen Wang、Teng-Wei Zhu、Le-Mao Yu、Jian-Wen Chen、Lu-Xia Wang、Lei Shi、Ding Li、Lian-Quan Gu、Zhi-Shu Huang、Lin-Kun An

  DOI：10.1016/j.ejmech.2016.12.054

  日期：2017.2

  low bioavailability in vivo possibly due to its low solubility in water. In order to obtain the derivatives with higher anti-MRSA activity and good water solubility, twenty eight bromo-substituted indolizinoquinoline-5,12-dione derivatives were synthesized in the present study. The antibacterial activity of the synthesized compounds was evaluated against one gram-negative and some gram-positive bacterial

  在我们之前的研究中，发现9-溴吲哚并喹啉-5,12-二酮1是一种良好的抗MRSA药物。然而，由于其在水中的低溶解度，它在体内的生物利用度非常低。为了获得具有较高的抗MRSA活性和良好的水溶性的衍生物，本研究合成了28个溴取代的吲哚并喹啉-5，12-二酮衍生物。评估了合成化合物对一种革兰氏阴性和某些革兰氏阳性细菌菌株（包括100株临床MRSA菌株）的抗菌活性。的UV测定法进行，以确定六个活性化合物的溶解度16，21，23和27-29。最有效的化合物28表现出对临床MRSA菌株的强活性，MIC 50和MIC 90值均低于7.8 ng / mL。化合物27具有1.98 mg / mL的良好水溶性，并且对临床MRSA菌株具有很强的活性，MIC 50值为63 ng / mL，MIC 90值为125 ng / mL，比万古霉素高16倍。
• The synthesis of furoquinolinedione and isoxazoloquinolinedione derivatives as selective Tyrosyl-DNA phosphodiesterase 2 (TDP2) inhibitors
  作者：Hao Yang、Xiao-Qing Zhu、Wenjie Wang、Yu Chen、Zhu Hu、Yu Zhang、De-Xuan Hu、Le-Mao Yu、Keli Agama、Yves Pommier、Lin-Kun An

  DOI：10.1016/j.bioorg.2021.104881

  日期：2021.6

  Based on our previous study on the development of the furoquinolinedione and isoxazoloquinolinedione TDP2 inhibitors, the further structure-activity relationship (SAR) was studied in this work. A series of furoquinolinedione and isoxazoloquinolinedione derivatives were synthesized and tested for enzyme inhibitions. Enzyme-based assays indicated that isoxazoloquinolinedione derivatives selectively showed

  基于我们之前对呋喃喹啉二酮和异恶唑并喹啉二酮 TDP2 抑制剂开发的研究，本工作进一步研究了构效关系 (SAR)。合成了一系列呋喃喹啉二酮和异恶唑并喹啉二酮衍生物并测试了酶抑制作用。基于酶的测定表明，异恶唑并喹啉二酮衍生物在亚微摩尔范围内选择性地显示出高 TDP2 抑制活性，呋喃喹啉二酮衍生物在低微摩尔范围内选择性地显示出高 TDP2 抑制活性。最有效的 3-(3,4-二甲氧基苯基) 异恶唑并[4,5-g]喹啉-4,9-二酮 ( 70 ) 显示出 TDP2 抑制活性，IC 50为 0.46 ± 0.15 μM。这项工作将促进未来发现异恶唑并喹啉二酮 TDP2 选择性抑制剂的努力。
• Han, Gyoonhee; Shin, Kye Jung; Kim, Dong Chan, Heterocycles, 1996, vol. 43, # 11, p. 2495 - 2502
  作者：Han, Gyoonhee、Shin, Kye Jung、Kim, Dong Chan、Yoo, Kyung Ho、Kim, Dong Jin、Park, Sang Woo

  DOI：——

  日期：——
• Streptonigrin. 1. Structure-activity relationships among simple bicyclic analogs. Rate dependence of DNA degradation on quinone reduction potential
  作者：Iftikhar A. Shaikh、Francis Johnson、Arthur P. Grollman

  DOI：10.1021/jm00158a002

  日期：1986.8

  A series of simple aza and diaza bicyclic quinones related to the AB ring system of streptonigrin (1) have been synthesized and tested in vitro for their ability to degrade DNA under conditions similar to those used with the parent drug. The results obtained from a study of 22 quinones indicate that there is a quantitative linear relationship between their reduction potentials and the rate at which they degrade DNA under identical conditions in vitro. Almost all of the synthetic substances were superior to 1 in their DNA-degrading ability.
• Synthesis and Cytotoxicity of 2-Methyl-4,9-dihydro-1-substituted-1<i>H</i>-imidazo[4,5-<i>g</i>]quinoxaline-4,9-diones and 2,3-Disubstituted-5,10-pyrazino[2,3-<i>g</i>]quinoxalinediones
  作者：Hee-Won Yoo、Myung-Eun Suh、Sang Woo Park

  DOI：10.1021/jm970695n

  日期：1998.11.1

  Series of 2-methyl-4,9-dihydro-1H-imidazo[4,5-g]quinoxaline-4,9-diones and 5,10-pyrazino[2,3g]quinoxalinediones have been synthesized from 6,7-dichloro-5,8-quinoxalinedione for developing new anticancer drugs. Intercalation complex of 2-methyl-4,9-dihydro-1-methyl-1H-imidazo-[4,5-g]quinoxaline-4,9-dione with GC/GC base pairs by a computer graphics-aided method was parallel to the axis of the helix. The interaction energies of synthetic compounds were low. 2-Methyl-4,9-dihydro-1-(4-bromophenyl)-1H-imidazo[4,5-g]quinoxaline-4,9-dione, which has the lowest interaction energy of the test compounds, was identified as being more cytotoxic against human gastric adenocarcinoma cells (MKN 45) than adriamycin and cis-platin in vitro using the MTT assay. The IC50 value of this compound was 1.30 mu M, whereas those of adriamycin and cis-platin were 3.13 and 86.5 mu M, respectively. The cytotoxicity of 2,3-diethyl-5,10-pyrazino-[2,3-g]quinoxalinedione was comparable to that of adriamycin in the in vitro assay. However these compounds showed loss of activity on human lung adenocarcinoma cells (PC 14) and human colon adenocarcinoma cells (colon 205). These results suggest that 2-methyl-4,9-dihydrol-(4-bromophenyl)-1H-imidazo[4,5-g]quinoxaline-4,9-dione, with the lowest interaction energy, might be an excellent and selective antitumor agent against MKN 45.