10-Amino-2-(2-dimethylamino-ethyl)-dibenzo[de,h]isoquinoline-1,3-dione | 140917-87-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: 10-Amino-2-(2-dimethylamino-ethyl)-dibenzo[de,h]isoquinoline-1,3-dione
• 英文别名: 4-Amino-15-[2-(dimethylamino)ethyl]-15-azatetracyclo[7.7.1.02,7.013,17]heptadeca-1(17),2(7),3,5,8,10,12-heptaene-14,16-dione
• CAS: 140917-87-9
• 化学式: C₂₀H₁₉N₃O₂
• 分子量: 333.39
• InChiKey: SGGNFDSEAJVHLN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 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：
  66.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  10-Amino-2-(2-dimethylamino-ethyl)-dibenzo[de,h]isoquinoline-1,3-dione 在 硫酸 、 铜 、 溶剂黄146 、 sodium nitrite 作用下， 生成 2-(2-Dimethylamino-ethyl)-10-nitro-dibenzo[de,h]isoquinoline-1,3-dione
  参考文献：
  名称：

  2- [2'-（二甲氨基）乙基] -1，2-二氢-3H-二苯并[de，h]异喹啉-1,3-二酮，在4、8、9、10和11位具有取代基。抗肿瘤活性和定量构效关系。

  摘要：

  新的2- [2'-（二甲基氨基）乙基] -1,2-二氢-3H-二苯并[de，h]异喹啉-1,3-二酮在4、8、9、10和11位带有取代基合成的。由氨基氮杂胺制备的重氮盐是许多类似物的关键中间体。在包括人类黑素瘤和卵巢癌以及鼠L1210白血病在内的一系列肿瘤细胞中，六种新化合物比阿扎那非更有效。这些化合物中的三种，即10-OCH3、10-OC2H5和10-F类似物，其心脏毒性与肿瘤细胞毒性的比率比阿扎那非好。八种化合物对MDR L1210白血病没有交叉耐药性，而且10-CN类似物对实体瘤细胞的作用比对白血病细胞的作用更强。9-OH，10-CN，和10-F类似物对MFX 7乳腺癌和WiDr结肠癌以及敏感性A599肺癌的敏感和耐药细胞系均具有高效力。在小鼠的P388白血病中，10-Cl，10-NH2和10-CN类似物优于阿扎那非的优势是显而易见的，在这种测定中，10-CN类似物比阿霉素更有效。定

  DOI：

  10.1021/jm960623g
• 作为产物：
  描述：

  N-[2-(2-Dimethylamino-ethyl)-1,3-dioxo-2,3-dihydro-1H-dibenzo[de,h]isoquinolin-10-yl]-2,2-dimethyl-propionamide 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以76%的产率得到10-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

文献信息

• COMPOSITIONS AND METHODS TO IMPROVE THE THERAPEUTIC BENEFIT OF SUBOPTIMALLY ADMINISTERED CHEMICAL COMPOUNDS INCLUDING SUBSTITUTED NAPHTHALIMIDES SUCH AS AMONAFIDE FOR THE TREATMENT OF IMMUNOLOGICAL, METABOLIC, INFECTIOUS, AND BENIGN OR NEOPLASTIC HYPERPROLIFERATIVE DISEASE CONDITIONS
  申请人：BROWN Dennis M.

  公开号：US20160067241A1

  公开（公告）日：2016-03-10

  The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutic agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to naphthalimides such as amonafide or analogs, derivatives, or prodrugs thereof.
• 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.
• 2-[2‘-(Dimethylamino)ethyl]-1,2-dihydro-3<i>H</i>-dibenz[<i>de</i>,<i>h</i>]isoquinoline-1,3-diones with Substituents at Positions 4, 8, 9, 10, and 11. Synthesis, Antitumor Activity, and Quantitative Structure−Activity Relationships
  作者：Salah M. Sami、Robert T. Dorr、David S. Alberts、Anikó M. Sólyom、William A. Remers

  DOI：10.1021/jm960623g

  日期：1996.1.1

  New 2-[2'-(dimethylamino)ethyl]-1,2-dihydro-3H-dibenz[de,h]isoquinoline-1,3- diones with substituents at the 4, 8, 9, 10, and 11 positions were synthesized. Diazonium salts prepared from aminoazonafides were key intermediates for many of the analogues. Six of the new compounds were more potent than azonafide in a panel of tumor cells including human melanoma and ovarian carcinoma and murine L1210 leukemias

  新的2- [2'-（二甲基氨基）乙基] -1,2-二氢-3H-二苯并[de，h]异喹啉-1,3-二酮在4、8、9、10和11位带有取代基合成的。由氨基氮杂胺制备的重氮盐是许多类似物的关键中间体。在包括人类黑素瘤和卵巢癌以及鼠L1210白血病在内的一系列肿瘤细胞中，六种新化合物比阿扎那非更有效。这些化合物中的三种，即10-OCH3、10-OC2H5和10-F类似物，其心脏毒性与肿瘤细胞毒性的比率比阿扎那非好。八种化合物对MDR L1210白血病没有交叉耐药性，而且10-CN类似物对实体瘤细胞的作用比对白血病细胞的作用更强。9-OH，10-CN，和10-F类似物对MFX 7乳腺癌和WiDr结肠癌以及敏感性A599肺癌的敏感和耐药细胞系均具有高效力。在小鼠的P388白血病中，10-Cl，10-NH2和10-CN类似物优于阿扎那非的优势是显而易见的，在这种测定中，10-CN类似物比阿霉素更有效。定