N-[2-(二甲氨基)乙基]-9-羰基-9,10-二氢吖啶-4-甲酰胺 | 103554-58-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: N-[2-(二甲氨基)乙基]-9-羰基-9,10-二氢吖啶-4-甲酰胺
• 英文名称: N-<2-(dimethylamino)ethyl>-9,10-dihydro-9-oxo-4-acridinecarboxamide
• 英文别名: N-[2-(dimethylamino)ethyl]-9,10-dihydro-9-oxo-4-acridinecarboxamide；4-Acridinecarboxamide, 9,10-dihydro-N-(2-(dimethylamino)ethyl)-9-oxo-；N-[2-(dimethylamino)ethyl]-9-oxo-10H-acridine-4-carboxamide
• CAS: 103554-58-1
• 化学式: C₁₈H₁₉N₃O₂
• 分子量: 309.368
• InChiKey: PYNUPZKQDKYVMH-UHFFFAOYSA-N

物化性质

• 熔点：
  171-173 °C(Solv: toluene (108-88-3))
• 沸点：
  487.0±45.0 °C(Predicted)
• 密度：
  1.209±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  61.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-[2-(二甲氨基)乙基]-9-羰基-9,10-二氢吖啶-4-甲酰胺 在 氯化亚砜 作用下， 生成 9-氯-N-[2-(二甲氨基)乙基]吖啶-4-甲酰胺
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Potential Anticancer Agents:  Alkylcarbamates of 3-(9-Acridinylamino)-5-hydroxymethylaniline

  摘要：

  A series of potential 9-anilinoacridine antitumor agents, 3-(9-acridinylamino)-5-hydroxymethylaniline (AHMA) derivatives with monosubstituent at C4' and disubstituents at C4' and C5' of the acridine ring and their alkylcarbamates, were synthesized for evaluation of their antitumor activity. A structure-activity relationship (SAR) study showed that the AHMA-alkylcarbamates were more potent than their corresponding parent AHMA compounds. In addition, the cytotoxicity of the AHMA-alkylcarbamate decreased with increasing length and size of the alkyl function. Among these compounds, AHMA-ethylcarbamate (18) and 4'-methyl-5'-dimethylaminoethylcarboxamido-AHMA-ethylcarbamate (34) possess potent cytotoxicity on the inhibition of human leukemic HL-60 cell growth in culture. Further in vivo studies of these compounds displayed significant anticancer therapeutic effects in mice bearing sarcoma 180, Lewis lung carcinoma, and P388 leukemia.

  DOI：

  10.1021/jm9901226
• 作为产物：
  描述：

  4-羧基-9-茚酮 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-[2-(二甲氨基)乙基]-9-羰基-9,10-二氢吖啶-4-甲酰胺
  参考文献：
  名称：

  Synthesis and Evaluation of Novel Pyrimido-Acridone, -Phenoxadine, and -Carbazole as Topoisomerase II Inhibitors

  摘要：

  作为一系列研究新型拓扑异构酶 II 抑制剂的研究的一部分，合成了新型的吡啶并氨基醌、吡啶并苯氧烷和吡啶并氮杂茚，并评估了其体外和体内的抗肿瘤活性，以及作为拓扑异构酶 II-DNA 可裂解复合物形成指标的 DNA-蛋白质和/或 DNA-拓扑异构酶 II 交联活性。吡啶并氮杂茚具有较高的体外和体内效能。化合物 26（ER-37326），8-乙酰-2-[2-(二甲氨基)乙基]-1H-吡啶并[5,6,1-jk]氮杂茚-1,3(2H)-二酮，显示出对小鼠白血病 P388 和人类口腔癌 KB 的体外增殖抑制活性，IC50 值分别为 0.049 μM 和 0.35 μM。在体内，该化合物对植入小鼠的鼠肉瘤 M5076 的肿瘤生长抑制率为 T/C 值在 3.13 mg/kg/d 和 6.25 mg/kg/d 时分别为 42% 和 13%，且对体重没有显著影响。此外，化合物 26（ER-37326）增加了 P388 细胞中 DNA-拓扑异构酶 II 的交联形成。

  DOI：

  10.1248/cpb.52.1071

文献信息

• Potential antitumor agents. 54. Chromophore requirements for in vivo antitumor activity among the general class of linear tricyclic carboxamides
  作者：Brian D. Palmer、Gordon W. Rewcastle、Graham J. Atwell、Bruce C. Baguley、William A. Denny

  DOI：10.1021/jm00399a003

  日期：1988.4

  thioxanthenone, anthraquinone, pyridoquinazoline, dibenzodioxin, thianthrene, phenothiazine, phenoxazine, dibenzofuran, carbazole, and pyridoindole) of the general class of N-[2-(dimethylamino)ethyl] linear tricyclic carboxamides. Only the compounds containing coplanar chromophores intercalated DNA. There is an absolute requirement for an oxygen or aromatic nitrogen (possibly as hydrogen-bond acceptors) peri to

  报道了一般结构的许多不同实例（ac啶，吩嗪，蒽，a啶、,吨酮，噻吨酮，蒽醌，吡啶并喹唑啉，二苯并二恶英，噻吨，吩噻嗪，吩恶嗪，二苯并呋喃，咔唑和吡啶基吲哚的结构-抗肿瘤活性关系。 N- [2-（二甲基氨基）乙基]线性三环羧酰胺。仅包含共面发色团的化合物插入DNA。绝对需要羧酰胺周围的氧或芳族氮（可能是氢键受体），以及用于生物活性的平面环几何形状。除了进一步描述这类化合物的药效基团的性质外，该工作还确定了二苯并[1,4]二恶英是一种具有体内抗肿瘤活性的新型DNA嵌入发色团。
• New acridone-4-carboxylic acid derivatives as potential inhibitors of Hepatitis C virus infection
  作者：Anna Stankiewicz-Drogon、Larisa G. Palchykovska、Valentina G. Kostina、Inna V. Alexeeva、Anatoly D. Shved、Anna M. Boguszewska-Chachulska

  DOI：10.1016/j.bmc.2008.08.074

  日期：2008.10

  A new class of compounds - acridone derivatives - was tested using the direct fluorometric helicase activity assay to determine the inhibitory properties of the derivatives towards the NS3 helicase of Hepatitis C virus (HCV). The compounds were also tested as putative transcription inhibitors of in vitro transcription based on the DNA-dependent T7 RNA polymerase. Most of the acridone derivatives tested were transcription inhibitors; however, only four of them inhibited the NS3 helicase at low concentrations (IC50 from 3 mu M to 20 mu M) and were therefore selected for further studies on the mechanism of inhibition. The acridone derivatives probably act via intercalation into double- stranded nucleic acids but they may also interact directly with viral enzymes. Selected carboxamides were tested in the subgenomic HCV replicon system. Two of the compounds: N-(pyridin-4-yl)-amide and N-(pyridin-2-yl)-amide of acridone-4-carboxylic acid are efficient RNA replication inhibitors with selectivity indexes of 19.4 and 40.5, respectively, proving that the acridone derivatives may be regarded as potential antiviral agents. (C) 2008 Elsevier Ltd. All rights reserved.
• Antonini; Cola; Martelli, Il Farmaco, 1992, vol. 47, # 7-8, p. 1035 - 1046
  作者：Antonini、Cola、Martelli、Cholody、Konopa

  DOI：——

  日期：——
• Hicks, Kevin O.; Pruijn, Frederik B.; Baguley, Bruce C., Journal of Pharmacology and Experimental Therapeutics, 2001, vol. 297, # 3, p. 1088 - 1098
  作者：Hicks, Kevin O.、Pruijn, Frederik B.、Baguley, Bruce C.、Wilson, William R.

  DOI：——

  日期：——
• Synthesis and Evaluation of Novel Pyrimido-Acridone, -Phenoxadine, and -Carbazole as Topoisomerase II Inhibitors
  作者：Junichi Kamata、Toshimi Okada、Yoshihiko Kotake、Jun Niijima、Katsuji Nakamura、Toshimitsu Uenaka、Atsumi Yamaguchi、Kappei Tsukahara、Takeshi Nagasu、Nozomu Koyanagi、Kyosuke Kitoh、Kentaro Yoshimatsu、Hiroshi Yoshino、Hiroyuki Sugumi

  DOI：10.1248/cpb.52.1071

  日期：——

  As part of a series of studies to discover new topoisomerase II inhibitors, novel pyrimidoacridones, pyrimidophenoxadines, and pyrimidocarbazoles were synthesized, and in vitro and in vivo antitumor activities and DNA-protein and/or DNA-topoisomerase II cross-linking activity as an indicator of topoisomerase II-DNA cleavable complex formation were evaluated. The pyrimidocarbazoles possessed high in vitro and in vivo potencies. Compound 26 (ER-37326), 8-acetyl-2-[2-(dimethylamino)ethyl]-1H-pyrimido[5,6,1-jk]carbazole-1,3(2H)-dione, showed in vitro growth inhibitory activity with respective IC50 values of 0.049 μM and 0.35 μM against mouse leukemia P388 and human oral cancer KB. In vivo, this compound inhibited the tumor growth of mouse sarcoma M5076 implanted into mice with T/C values of 42% and 13% at 3.13 and 6.25 mg/kg/d respectively without significantly affecting the body weight. In addition, compound 26 (ER-37326) increased the formation of DNA-topoisomerase II cross-linking in P388 cells.

  作为一系列研究新型拓扑异构酶 II 抑制剂的研究的一部分，合成了新型的吡啶并氨基醌、吡啶并苯氧烷和吡啶并氮杂茚，并评估了其体外和体内的抗肿瘤活性，以及作为拓扑异构酶 II-DNA 可裂解复合物形成指标的 DNA-蛋白质和/或 DNA-拓扑异构酶 II 交联活性。吡啶并氮杂茚具有较高的体外和体内效能。化合物 26（ER-37326），8-乙酰-2-[2-(二甲氨基)乙基]-1H-吡啶并[5,6,1-jk]氮杂茚-1,3(2H)-二酮，显示出对小鼠白血病 P388 和人类口腔癌 KB 的体外增殖抑制活性，IC50 值分别为 0.049 μM 和 0.35 μM。在体内，该化合物对植入小鼠的鼠肉瘤 M5076 的肿瘤生长抑制率为 T/C 值在 3.13 mg/kg/d 和 6.25 mg/kg/d 时分别为 42% 和 13%，且对体重没有显著影响。此外，化合物 26（ER-37326）增加了 P388 细胞中 DNA-拓扑异构酶 II 的交联形成。