3-N,N-dimethylaminomethyl-4,11-dimethoxynaphtho[2,3-f]indole-5,10-dione | 222983-39-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: 3-N,N-dimethylaminomethyl-4,11-dimethoxynaphtho[2,3-f]indole-5,10-dione
• 英文别名: 4,11-dimethoxy-3-N,N-dimethylaminomethylnaphtho<2,3-f>indole-5,10-dione；4,11-dimethoxy-3-[(dimethylamino)methyl]-1H-naphtho[2,3-f]indole-5,10-dione；3-((dimethylamino)methyl)-4,11-dihydroxy-1H-naphtho[2,3-f]indole-5,10-dione；3-[(dimethylamino)methyl]-4,11-dimethoxy-1H-naphtho[2,3-f]indole-5,10-dione
• CAS: 222983-39-3
• 化学式: C₂₁H₂₀N₂O₄
• 分子量: 364.401
• InChiKey: ZTGNDYNQTWPYKQ-UHFFFAOYSA-N

物化性质

• 沸点：
  599.1±50.0 °C(Predicted)
• 密度：
  1.319±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  71.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-N,N-dimethylaminomethyl-4,11-dimethoxynaphtho[2,3-f]indole-5,10-dione 在 sodium methylate 、 sodium acetate 作用下， 以 甲醇 为溶剂， 反应 0.5h， 生成
  参考文献：
  名称：

  4,11-二氨基萘[2,3-f]吲哚-5,10-二酮的合成及构效关系研究。

  摘要：

  我们描述了4,11-二氨基萘[2,3-f]吲哚-5,10-二酮衍生物的合成及其对人肿瘤细胞的细胞毒性，这些细胞表达改变的抗癌药物反应的主要决定因素，外排泵P糖蛋白，和无功能的p53。用各种乙二胺对4,11-二甲氧基萘[2,3-f]吲哚-5,10-二酮中的甲氧基进行亲核取代，得到4,11-二氨基萘[2,3-f]吲哚-5,10-的衍生物二酮，其吲哚含有抗肿瘤药金刚酮的类似物。新化合物对表达多药耐药性，表达P-糖蛋白的肿瘤细胞的细胞毒性高度依赖于乙二胺部分末端氨基处的N-取代基。相对于野生型p53，p53无效结肠癌细胞对参考药物阿霉素的敏感性较低，

  DOI：

  10.1016/j.bmc.2006.03.052
• 作为产物：
  描述：

  N,N-二甲基氯烯亚胺 、 4,11-dimethoxynaphtho[2,3-f]indole-5,10-dione 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以85%的产率得到3-N,N-dimethylaminomethyl-4,11-dimethoxynaphtho[2,3-f]indole-5,10-dione
  参考文献：
  名称：

  Naphthoindoles. 8. Electrophilic substitution reactions of 4,11-dimethyxynaphtho[2,3-f]indole-5,10-dione

  摘要：

  DOI：

  10.1007/bf02251688

文献信息

• ——
  作者：A. E. Shchekotikhin、E. P. Baberkina、K. F. Turchin、V. N. Buyanov、N. N. Suvorov

  DOI：10.1023/a:1012727331823

  日期：——
• Synthesis and evaluation of new antitumor 3-aminomethyl-4,11-dihydroxynaphtho[2,3-f]indole-5,10-diones
  作者：Andrey E. Shchekotikhin、Valeria A. Glazunova、Lyubov G. Dezhenkova、Yuri N. Luzikov、Vladimir N. Buyanov、Helena M. Treshalina、Nina A. Lesnaya、Vladimir I. Romanenko、Dmitry N. Kaluzhny、Jan Balzarini、Keli Agama、Yves Pommier、Alexander A. Shtil、Maria N. Preobrazhenskaya

  DOI：10.1016/j.ejmech.2014.09.021

  日期：2014.10

  A series of new 3-aminomethyl-4,11-dihydroxynaphtho[2,3-f]indole-5,10-diones 6-13 bearing the cyclic diamine in the position 3 of the indole ring was synthesized. The majority of new compounds demonstrated a superior cytotoxicity than doxorubicin against a panel of mammalian tumor cells with determinants of altered drug response, that is, Pgp expression or p53 inactivation. For naphtho[2,3-f] indole-5,10-diones 6-9 bearing 3-aminopyrrolidine in the side chains, the ability to bind double-stranded DNA and inhibit topoisomerases 1 and 2 mediated relaxation of supercoiled DNA were demonstrated. Only one isomer, (R)-4,11-dihydroxy-3-((pyrrolidin-3-ylamino)methyl)-1H-naphtho[2,3-f]indole-5,10-dione (7) induced the formation of specific DNA cleavage products similar to the known topoisomerase 1 inhibitors camptothecin and indenoisoquinoline MJ-III-65, suggesting a role of the structure of the side chain of 3-aminomethylnaphtho[2,3-f]indole-5,10-diones in interaction with the target. Compound 7 demonstrated an antitumor activity in mice with P388 leukemia transplants whereas its enantiomer 6 was inactive. Thus, 3-aminomethyl derivatives of 4,11-dihydroxynaphtho[2,3-f] indole-5,10-dione emerge as a new prospective chemotype for the search of antitumor agents. (C) 2014 Elsevier Masson SAS. All rights reserved.
• Naphthoindole-based analogues of tryptophan and tryptamine: Synthesis and cytotoxic properties
  作者：Andrey E. Shchekotikhin、Lyubov G. Dezhenkova、Olga Yu. Susova、Valeria A. Glazunova、Yuri N. Luzikov、Yuri B. Sinkevich、Vladimir N. Buyanov、Alexander A. Shtil、Maria N. Preobrazhenskaya

  DOI：10.1016/j.bmc.2007.01.034

  日期：2007.4

  The efficacy of anthracycline based anticancer drugs is limited by pleiotropic drug resistance of tumor cells. Aiming at the design of anthracyclinone congeners capable of circumventing drug resistance, we synthesized naphthoindole containing derivatives of tryptophan and tryptamine. In doing so we adapted the traditional, gramine based approach for tryptophan and tryptamine synthesis. The most potent new compound, 3-(2-aminoethyl)-4,11-dihydroxynaphtho[2,3-Aindole-5,10-dione (16), was equally cytotoxic (IC50 within low micromolar concentrations) for human K562 leukemia and HCT116 colon carcinoma cell lines and their isogenic sublines with genetically defined determinants of altered drug response, that is, the expression of the multidrug transporter P-glycoprotein and loss of pro-apoptotic p53. Each of these mechanisms conferred resistance to the reference drug adriamycin. In contrast, naphthotryptamine 16, although less potent than adriamycin, was equally toxic for wild type cell lines and drug resistant counterparts. Moreover, at 3-5 mu M 16 inhibited topoisomerase I in vitro. Thus, our novel naphthoindole based derivative of tryptamine gained new activities important for anticancer therapy, namely, suppression of topoisomerase I and the ability to overcome resistance mediated by P-glycoprotein expression and p53 dysfunction. (c) 2007 Elsevier Ltd. All rights reserved.