2-[2-(dimethylamino)ethyl]-11-nitro-1H-dibenzo[de,h]isoquinoline-1,3(2H)-dione | 140917-75-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: 2-[2-(dimethylamino)ethyl]-11-nitro-1H-dibenzo[de,h]isoquinoline-1,3(2H)-dione
• 英文别名: 15-[2-(Dimethylamino)ethyl]-3-nitro-15-azatetracyclo[7.7.1.02,7.013,17]heptadeca-1(17),2(7),3,5,8,10,12-heptaene-14,16-dione
• CAS: 140917-75-5
• 化学式: C₂₀H₁₇N₃O₄
• 分子量: 363.373
• InChiKey: QKANXVQSRQMWOM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  27
• 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：
  86.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-[2-(dimethylamino)ethyl]-11-nitro-1H-dibenzo[de,h]isoquinoline-1,3(2H)-dione 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以62%的产率得到11-aminoazonafide
  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：

  anthracene-1,9-dicarboxylic acid anhydride 、 N,N-二甲基乙二胺 在 硫酸 、 硝酸 作用下， 生成 2-[2-(dimethylamino)ethyl]-11-nitro-1H-dibenzo[de,h]isoquinoline-1,3(2H)-dione 、 2-[2-(dimethylamino)ethyl]-8-nitro-1H-dibenzo[de,h]isoquinoline-1,3(2H)-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

• Azonafide derivatives, methods for their production and pharmaceutical compositions therefrom
  申请人：Unibioscreen S.A.

  公开号：EP1787985A1

  公开（公告）日：2007-05-23

  Azonafide derivatives are obtained by reacting azonafide with aldehydes, acyl halides, thioacyl halides, monoisocyanates, isothiocyanates or polyamines, and are useful as active ingredients of pharmaceutical compositions for the treament of cell proliferative disorders.

  Azonafide衍生物是通过将azonafide与醛类、酰卤、硫酰卤、单异氰酸酯、异硫氰酸酯或多胺反应而得到的，它们可作为药物组合物的有效成分，用于治疗细胞增殖性疾病。
• Azonafide Derivatives, Methods for Their Production and Pharmaceutical Compositions Therefrom
  申请人：Van Quaquebeke Eric

  公开号：US20080292585A1

  公开（公告）日：2008-11-27

  Azonafide derivatives are obtained by reacting azonafide with aldehydes, acyl halides, thioacyl halides, monoisocyanates, isothiocyanates, sulfonyl halides, monohalogenoalkanes, monohalogenoalkenes or monohalogenoalkynes, and are useful as active ingredients of pharmaceutical compositions for the prevention and treatment of cell proliferative disorders, in particular several forms of Cancer.

  Azonafide衍生物是通过将azonafide与醛类、酰卤、硫酰卤、单异氰酸酯、异硫氰酸酯、磺酰卤、单卤代烷烃、单卤代烯烃或单卤代炔烃反应得到的，并且它们可用作制药组合物的活性成分，用于预防和治疗细胞增殖性疾病，特别是几种癌症。
• 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.
• US7741337B2
  申请人：——

  公开号：US7741337B2

  公开（公告）日：2010-06-22
• [EN] AZONAFIDE DERIVATIVES, METHODS FOR THEIR PRODUCTION AND PHARMACEUTICAL COMPOSITIONS THEREFROM<br/>[FR] DERIVES D'AZONAFIDE, LEURS PROCEDES DE PRODUCTION ET LES COMPOSITIONS PHARMACEUTIQUES QUI LES CONTIENNENT
  申请人：UNIBIOSCREEN SA

  公开号：WO2007054292A2

  公开（公告）日：2007-05-18

  [EN] Azonafide derivatives are obtained by reacting azonafide with aldehydes, acyl halides, thioacyl halides, monoisocyanates, isothiocyanates, sulfonyl halides, monohalogenoalkanes, monohalogenoalkenes or monohalogenoalkynes, and are useful as active ingredients of pharmaceutical compositions for the prevention and treament of cell proliferative disorders, in particular several forms of Cancer.
  [FR] La présente invention concerne des dérivés d'azonafide préparés en faisant réagir de l'azonafide avec des aldéhydes, des halogénures d'acyle, des halogénures de thioacyle, des monoisocyanates, des isothiocyanates, des halogénures de sulfonyle, des monohalogénoalcanes, des monohalogénoalcènes ou des monohalogénoalcynes. Lesdits dérivés d'azonafide sont utilisables en tant que matière active dans des compositions pharmaceutiques destinées à la prévention et au traitement de dérèglements de la prolifération cellulaire, en particulier de plusieurs formes de cancer.