7-chloro-2-<2'-(dimethylamino)ethyl>-1,2-dihydro-3H-dibenzisoquinoline-1,3-dione | 140917-78-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: 7-chloro-2-<2'-(dimethylamino)ethyl>-1,2-dihydro-3H-dibenzisoquinoline-1,3-dione
• 英文别名: 8-Chloro-15-[2-(dimethylamino)ethyl]-15-azatetracyclo[7.7.1.02,7.013,17]heptadeca-1(17),2,4,6,8,10,12-heptaene-14,16-dione
• CAS: 140917-78-8
• 化学式: C₂₀H₁₇ClN₂O₂
• 分子量: 352.82
• InChiKey: XGYXHXPLVANWMB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-chloro-2-<2'-(dimethylamino)ethyl>-1,2-dihydro-3H-dibenzisoquinoline-1,3-dione 在 sodium azide 作用下， 以 乙醇 为溶剂， 以78%的产率得到7-Amino-2-(2-dimethylamino-ethyl)-dibenzo[de,h]isoquinoline-1,3-dione
  参考文献：
  名称：

  Amino-Substituted 2-[2-(Dimethylamino)ethyl]-1,2-dihydro-3H-dibenz[de,h]isoquinoline-1,3-diones. Synthesis, Antitumor Activity, and Quantitative Structure-Activity Relationship

  摘要：

  Sets of 2-[2'-(dimethylamino)ethyl]-1,2-dihydro-3H-dibenz[de,h]isoquinoline-1,3-diones with amino and actylamino groups at each of the eight positions on the anthracene nucleus were synthesized from appropriately substituted anthracenes. Their evaluation in in vitro antitumor and cardiotoxicity assays revealed a very strong dependence of potency on the position of substitution. Certain compounds, including the 4-, 5-, 7-, and 9-amino derivatives, showed significantly higher potency than the unsubstituted parent compound, azonafide. Among them, 7-aminoazonafide had low cardiotoxicity relative to cytotoxicity. In general, the acetylamino analogues were less potent than the amino derivatives against tumor cells and neonatal rat heart myocytes; however, 5-(acetylamino)azonafide was highly cardiotoxic. 9-Aminoazonafide was more efficacious than azonafide or amonafide against P388 leukemia in mice. Statistically significant correlations were made between the ability of amino analogues to increase the transition melt temperature (Delta T-m) of DNA and their potency against solid tumors, leukemia cells, or cardiac myocytes.

  DOI：

  10.1021/jm00006a018
• 作为产物：
  描述：

  N,N-二甲基乙二胺 、 10-chloroanthracene-1,9-dicarboxylic acid 以 甲苯 为溶剂， 反应 8.0h， 以69%的产率得到7-chloro-2-<2'-(dimethylamino)ethyl>-1,2-dihydro-3H-dibenzisoquinoline-1,3-dione
  参考文献：
  名称：

  Amino-Substituted 2-[2-(Dimethylamino)ethyl]-1,2-dihydro-3H-dibenz[de,h]isoquinoline-1,3-diones. Synthesis, Antitumor Activity, and Quantitative Structure-Activity Relationship

  摘要：

  Sets of 2-[2'-(dimethylamino)ethyl]-1,2-dihydro-3H-dibenz[de,h]isoquinoline-1,3-diones with amino and actylamino groups at each of the eight positions on the anthracene nucleus were synthesized from appropriately substituted anthracenes. Their evaluation in in vitro antitumor and cardiotoxicity assays revealed a very strong dependence of potency on the position of substitution. Certain compounds, including the 4-, 5-, 7-, and 9-amino derivatives, showed significantly higher potency than the unsubstituted parent compound, azonafide. Among them, 7-aminoazonafide had low cardiotoxicity relative to cytotoxicity. In general, the acetylamino analogues were less potent than the amino derivatives against tumor cells and neonatal rat heart myocytes; however, 5-(acetylamino)azonafide was highly cardiotoxic. 9-Aminoazonafide was more efficacious than azonafide or amonafide against P388 leukemia in mice. Statistically significant correlations were made between the ability of amino analogues to increase the transition melt temperature (Delta T-m) of DNA and their potency against solid tumors, leukemia cells, or cardiac myocytes.

  DOI：

  10.1021/jm00006a018

文献信息

• 6- and 7-Substituted 2-[2‘-(Dimethylamino)ethyl]-1,2-dihydro-3<i>H</i>- dibenz[<i>de</i>,<i>h</i>]isoquinoline-1,3-diones:  Synthesis, Nucleophilic Displacements, Antitumor Activity, and Quantitative Structure−Activity Relationships
  作者：Salah M. Sami、Robert T. Dorr、Anikó M. Sólyom、David S. Alberts、Bhashyam S. Iyengar、William A. Remers

  DOI：10.1021/jm950742g

  日期：1996.1.1

  New 2-[2'-(dimethylamino)ethyl]-3H-dibenz[de,h]isoquinoline-1,3-diones with substituents at the 6- and 7-positions were prepared. Nucleophilic aromatic displacement was a key reaction in the syntheses. Ten of the new compounds were more potent than the unsubstituted compound, azonafide, in a panel of tumor cells including human melanoma and ovarian cancer and murine sensitive and MDR L1210 leukemia

  制备了在6-和7-位具有取代基的新的2- [2'-（二甲基氨基）乙基] -3H-二苯并[de，h]异喹啉-1,3-二酮。亲核芳香族取代是合成中的关键反应。在包括人类黑素瘤和卵巢癌以及鼠类敏感和MDR L1210白血病在内的一系列肿瘤细胞中，十种新化合物比未取代的化合物azonafide更有效。它们在细胞培养中的心脏毒性也较小。这些化合物中的四种对MDR白血病不具有交叉耐药性，其中一种（6-乙氧基氮磺酰胺）对实体瘤细胞的效力几乎与白血病细胞一样。这些化合物对人乳腺癌，结肠癌和肺癌细胞（包括阿霉素和米托蒽醌抗性细胞株）也具有良好的效力。与阿佐那非相比，新类似物在体内的优势更小，但是6-乙氧基氮芥酸对小鼠的L1210白血病和皮下B16黑色素瘤更有效。尽管未发现细胞中抗肿瘤效力与取代基的理化性质之间的相关性，但在统计学上，DNA熔融转变温度（δTm）与实体肿瘤细胞以及对6取代的azonafides
• Amino-Substituted 2-[2-(Dimethylamino)ethyl]-1,2-dihydro-3H-dibenz[de,h]isoquinoline-1,3-diones. Synthesis, Antitumor Activity, and Quantitative Structure-Activity Relationship
  作者：Salah M. Sami、Robert T. Dorr、Aniko M. Solyom、David S. Alberts、William A. Remers

  DOI：10.1021/jm00006a018

  日期：1995.3

  Sets of 2-[2'-(dimethylamino)ethyl]-1,2-dihydro-3H-dibenz[de,h]isoquinoline-1,3-diones with amino and actylamino groups at each of the eight positions on the anthracene nucleus were synthesized from appropriately substituted anthracenes. Their evaluation in in vitro antitumor and cardiotoxicity assays revealed a very strong dependence of potency on the position of substitution. Certain compounds, including the 4-, 5-, 7-, and 9-amino derivatives, showed significantly higher potency than the unsubstituted parent compound, azonafide. Among them, 7-aminoazonafide had low cardiotoxicity relative to cytotoxicity. In general, the acetylamino analogues were less potent than the amino derivatives against tumor cells and neonatal rat heart myocytes; however, 5-(acetylamino)azonafide was highly cardiotoxic. 9-Aminoazonafide was more efficacious than azonafide or amonafide against P388 leukemia in mice. Statistically significant correlations were made between the ability of amino analogues to increase the transition melt temperature (Delta T-m) of DNA and their potency against solid tumors, leukemia cells, or cardiac myocytes.