N-[2-(dimethylamino)ethyl]-15-methyl-8-oxo-14-azatetracyclo[7.7.1.02,7.013,17]heptadeca-1(16),2(7),3,5,9(17),10,12,14-octaene-3-carboxamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: N-[2-(dimethylamino)ethyl]-15-methyl-8-oxo-14-azatetracyclo[7.7.1.02,7.013,17]heptadeca-1(16),2(7),3,5,9(17),10,12,14-octaene-3-carboxamide
• 化学式: C₂₂H₂₁N₃O₂
• 分子量: 359.428
• InChiKey: IAJMOHVDXKZZCN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  62.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-aminoanthraquinone-1-carbonitrile 在 sodium hydroxide 、 硫酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 11.0h， 生成 N-[2-(dimethylamino)ethyl]-15-methyl-8-oxo-14-azatetracyclo[7.7.1.02,7.013,17]heptadeca-1(16),2(7),3,5,9(17),10,12,14-octaene-3-carboxamide
  参考文献：
  名称：

  Synthesis and cytotoxic activity of N-[(alkylamino)alkyl]carboxamide derivatives of 7-oxo-7H-benz[de]anthracene, 7-oxo-7H-naphtho[1,2,3-de]quinoline, and 7-oxo-7H-benzo[e]perimidine

  摘要：

  7-Oxo-7H-naphtho[1,2,3-de]quinoline-11-carboxamides and analogues were prepared and evaluated for in vitro and in vivo antitumor activity. Chromophore variations included 'deaza' (7-oxo-7H-benz[de]anthracene) and 'diaza' (7-oxo-7H-benzo[e]perimidine) analogues, and side chain variations included chiral a-methyl compounds. The naphthoquinolines were the most cytotoxic, with IC50 values of 5-20 nM, and showed the strongest DNA binding, with high selectivity for G-C rich DNA. The chiral a-methyl analogues were 10-20-fold more cytotoxic than the parent des-methyl compound. Both enantiomers provided substantial growth delays against s.c. colon 38 tumors in mice, with the R-enantiomer more active than the S (tumor growth delays of >35 and 12 days, respectively). 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.03.033

文献信息

• Synthesis and Cytotoxic Activity of 7-Oxo-7<i>H</i>-dibenz[<i>f</i><i>,</i><i>i</i><i>j</i>]isoquinoline and 7-Oxo-7<i>H</i>-benzo[<i>e</i>]perimidine Derivatives
  作者：Xianyong Bu、Leslie W. Deady、Graeme J. Finlay、Bruce C. Baguley、William A. Denny

  DOI：10.1021/jm010041l

  日期：2001.6.1

  A series of 7-oxo-7H-dibenz[f,ij]isoquinoline and 7-oxo-7H-benzo[e]perimidines bearing cationic side chains were prepared from aminoanthraquinones. The perimidines were prepared from 1-aminoanthraquinone by initial condensation with urea or dimethylacetamide. A series of 2-, 4-, 8-, and 11-carboxy derivatives of the dibenzisoquinolines were prepared from aminoanthraquinonecarboxylic acids. The cationic

  从氨基蒽醌制备了一系列带有阳离子侧链的7-氧代-7H-二苯并[f，ij]异喹啉和7-氧代-7H-苯并[e]亚氨基。通过与尿素或二甲基乙酰胺的初始缩合，由1-氨基蒽醌制备过亚im啶。由氨基蒽醌羧酸制备了二苯并异喹啉的一系列2-，4-，8-和11-羧基衍生物。由这些经由酰胺，胺或亚甲基接头制备阳离子衍生物，以研究侧链定位对生物活性的影响。在一系列与羧酰胺连接的化合物中，增加的细胞毒性顺序为8-<4- <2- <11-。2-和4-羧酰胺对小鼠体内的皮下结肠38肿瘤表现出明显的生长延迟，
• Polycyclic amide compound, preparation process and use thereof
  申请人：HEBEI GRANDIOS PHARMA CO., LTD.

  公开号：US11046687B2

  公开（公告）日：2021-06-29

  A novel polycyclic amide compound, preparation process and use thereof are provided. The compound has cytotoxic biological activity, particularly for the treatment and/or prevention of cell proliferative diseases such as cancer. This compound is a compound represented by Formula I or a pharmaceutically acceptable salt, solvate, polymorph, enantiomer or racemic mixture, prodrug and N-oxide thereof, wherein, R, R1-R3 are independently selected from hydrogen, C1-5 alkyl, or C1-5 having a hydroxyl group or a halogen, and may be bonded to each other to form a ring, Z is an arbitrary substituent group, X1 and X2 may be carbon or nitrogen respectively, Q is oxygen or sulfur. Compared to the existing known polycyclic amide compounds, the novel polycyclic amide compound has more potent cytotoxicity and can be used for the treatment of diseases such as tumors, cancers, Alzheimer's disease, autoimmune diseases, cataracts, psychological disorders, depression and/or anxiety.

  本研究提供了一种新型多环酰胺化合物及其制备工艺和用途。该化合物具有细胞毒性生物活性，尤其适用于治疗和/或预防癌症等细胞增殖性疾病。该化合物是由式 I 或 一种药学上可接受的盐、溶液剂、多晶型、对映体或外消旋混合物、原药及其N-氧化物，其中，R、R1-R3独立选自氢、C1-5烷基或具有羟基或卤素的C1-5，并可相互键合形成环，Z为任意取代基，X1和X2可分别为碳或氮，Q为氧或硫。与现有已知的多环酰胺化合物相比，新型多环酰胺化合物具有更强的细胞毒性，可用于治疗肿瘤、癌症、阿尔茨海默病、自身免疫性疾病、白内障、心理障碍、抑郁症和/或焦虑症等疾病。
• Synthesis and cytotoxic activity of N-[(alkylamino)alkyl]carboxamide derivatives of 7-oxo-7H-benz[de]anthracene, 7-oxo-7H-naphtho[1,2,3-de]quinoline, and 7-oxo-7H-benzo[e]perimidine
  作者：Xianyong Bu、Junjie Chen、Leslie W. Deady、Clare L. Smith、Bruce C. Baguley、Debra Greenhalgh、Shangjin Yang、William A. Denny

  DOI：10.1016/j.bmc.2005.03.033

  日期：2005.6

  7-Oxo-7H-naphtho[1,2,3-de]quinoline-11-carboxamides and analogues were prepared and evaluated for in vitro and in vivo antitumor activity. Chromophore variations included 'deaza' (7-oxo-7H-benz[de]anthracene) and 'diaza' (7-oxo-7H-benzo[e]perimidine) analogues, and side chain variations included chiral a-methyl compounds. The naphthoquinolines were the most cytotoxic, with IC50 values of 5-20 nM, and showed the strongest DNA binding, with high selectivity for G-C rich DNA. The chiral a-methyl analogues were 10-20-fold more cytotoxic than the parent des-methyl compound. Both enantiomers provided substantial growth delays against s.c. colon 38 tumors in mice, with the R-enantiomer more active than the S (tumor growth delays of >35 and 12 days, respectively). 2005 Elsevier Ltd. All rights reserved.