N⁴-[2-(dimethylamino)ethyl]-1-chloro-9-oxo-9,10-dihydro-4-acridinecarboxamide | 165603-30-5

• 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
• 英文名称: N⁴-[2-(dimethylamino)ethyl]-1-chloro-9-oxo-9,10-dihydro-4-acridinecarboxamide
• 英文别名: 1-chloro-N-(2-(dimethylamino)ethyl)-9-oxo-9,10-dihydroacridine-4-carboxamide；1-Chloro-N-[2-(dimethylamino)ethyl]-9,10-dihydro-9-oxo-4-acridinecarboxamide；1-chloro-N-[2-(dimethylamino)ethyl]-9-oxo-10H-acridine-4-carboxamide
• CAS: 165603-30-5
• 化学式: C₁₈H₁₈ClN₃O₂
• 分子量: 343.813
• InChiKey: UBXITCMRCLDWFJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  24
• 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：

  N⁴-[2-(dimethylamino)ethyl]-1-chloro-9-oxo-9,10-dihydro-4-acridinecarboxamide 在 三乙胺 作用下， 以 乙二醇乙醚 为溶剂， 反应 4.0h， 生成 N-[2-(dimethylamino)ethyl]-1-[3-[3-(1,3-dioxobenzo[de]isoquinolin-2-yl)propyl-methylamino]propylamino]-9-oxo-10H-acridine-4-carboxamide
  参考文献：
  名称：

  Synthesis and Biological Evaluation of New Asymmetrical Bisintercalators as Potential Antitumor Drugs

  摘要：

  The good results obtained in the past decade with various types of potential bisintercalating agents, e. g., LU 79553, DMP 840, BisBFI, MCI3335, WMC-26, BisAC, BisPA, and the asymmetrical derivative WMC-79 ( Chart 1), prompted us to investigate a new series of asymmetrical bisintercalators, compounds 1a-t ( Chart 2), which can combine the potentiality of bisintercalation with a possible different mechanism of action due to two diverse chromophores. The DNA-binding properties of these compounds have been examined using fluorometric techniques: target compounds are excellent DNA ligands, with a clear preference for binding to AT-rich duplexes. In vitro cytotoxicity of these derivatives toward human hormone-refractory prostate adenocarcinoma cell line (PC-3) is described. Apoptosis assays of four selected compounds are also reported. Very potent cytotoxic compounds, some of them capable of inducing early apoptosis, have been identified.

  DOI：

  10.1021/jm0606793
• 作为产物：
  描述：

  氯苯扎利 在 硫酸 、 N,N'-羰基二咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 生成 N⁴-[2-(dimethylamino)ethyl]-1-chloro-9-oxo-9,10-dihydro-4-acridinecarboxamide
  参考文献：
  名称：

  一种氮杂芳环烷基氨基吖啶酮-4-酰胺类化合物 及其制备方法与应用

  摘要：

  本发明提供一种式I或式II所示的氮杂芳环烷基氨基吖啶酮-4-酰胺类化合物及其制备方法与应用。式I、式II中，R1为H、OCH3、OCH2CH3、OCH2CH2CH3、Cl、Br、CF3、NO2或碳原子数为1-5的直链烷基，R2为N(CH3)2或OCH3，R3为2-吡啶基、3-吡啶基、4-吡啶基、吲哚基、喹啉基、嘧啶基或吡嗪基，m＝1，2，3或4，n＝1，2，3或4。经过多种肿瘤细胞系测试(包括肝癌细胞，白血病细胞等)以及DNA连接，拓扑异构酶测试，证明本发明的化合物是一种潜在的具有DNA连接以及对拓扑异构酶有抑制活性的抗肿瘤药物。本发明提供的化合物原料易得，制备方法简单，实验证明其有良好的抗癌效果，在抗肿瘤药物设计研发领域有着良好的应用前景。

  公开号：

  CN104262327B

文献信息

• 1-[(ω-Aminoalkyl)amino]-4-[<i>N</i>-(ω-aminoalkyl)carbamoyl]-9-oxo-9,10-dihydro- acridines as Intercalating Cytotoxic Agents:  Synthesis, DNA Binding, and Biological Evaluation
  作者：Ippolito Antonini、Paolo Polucci、Terence C. Jenkins、Lloyd R. Kelland、Ernesto Menta、Nicoletta Pescalli、Barbara Stefanska、Jan Mazerski、Sante Martelli

  DOI：10.1021/jm970114u

  日期：1997.11.1

  A series of DNA-intercalating potential antitumor agents, 1-[(omega-aminoalkyl)amino]-4-[N-(omega-aminoalkyl)carbamoyl]-9-oxo-9, 10-dihydroacridines, has been prepared by aminolysis of the corresponding 4-[N-(omega-aminoalkyl)carbamoyl]-1-chloro derivative with a suitable omega-aminoalkylamine. The noncovalent DNA-binding properties of these bis-functionalized compounds have been examined using a combination

  一系列的DNA嵌入潜在的抗肿瘤药1-[（（ω-氨基烷基）氨基] -4- [N-（ω-氨基烷基）氨基甲酰基] -9-oxo-9，10-二氢ac啶，已经通过氨解法制备。相应的4- [N-（ω-氨基烷基）氨基甲酰基] -1-氯衍生物与合适的ω-氨基烷基胺。这些双功能化的化合物的非共价DNA结合特性已使用荧光和热变性技术的组合进行了检查，并与已建立的DNA嵌入剂和阳离子小沟配体的行为进行了比较。结果表明（i）这些药物的DNA亲和力比功能化程度较低的a啶酮高得多，其“表观”结合常数为（0.1-2.1）x 10（7）和（0.3-7.5）x 10（7）M- pH分别为5和7时为1，（ii）整体亲和力对柔性侧链的长度和所连接的胺取代基的复杂度均敏感，并且（iii）侧链侧链影响向中等AT优先结合的转换。尽管对某些化合物而言，很差的相关性，但对六种肿瘤细胞系的体外细胞毒性作用与观察到的DNA亲和力大致相似。还
• Synthesis, cytotoxic activities and proposed mode of binding of a series of bis{[(9-oxo-9,10-dihydroacridine-4-carbonyl)amino]alkyl}alkylamines
  作者：Miguel F Braña、Luis Casarrubios、Gema Domı́nguez、Carlos Fernández、José M Pérez、Adoración G Quiroga、Carmen Navarro-Ranninger、Beatriz de Pascual-Teresa

  DOI：10.1016/s0223-5234(02)01348-x

  日期：2002.4

  been tested against HT-29 cell lines. Compounds 6b and 6d showed an interesting cytotoxic profile and were subjected to further cytotoxic evaluation, DNA binding properties and molecular modelling studies. The evaluation of the cytotoxic activity of compounds 6b and 6d against pairs of cisplatin-sensitive and -resistant ovarian tumour cells shows that both compounds may be endowed with interesting antitumour

  已经制备了一系列双（[（（9-氧代-9,10-二氢ac啶-4-羰基氨基）烷基]烷基）烷基胺，并且已经针对HT-29细胞系测试了它们的抗增殖特性。化合物6b和6d显示出令人感兴趣的细胞毒性概况，并进行了进一步的细胞毒性评估，DNA结合特性和分子模型研究。对化合物6b和6d对顺铂敏感和耐药的卵巢肿瘤细胞对的细胞毒活性的评估表明，这两种化合物均具有有趣的抗肿瘤特性，因为它们能够绕过A2780cisR，CH1cisR和Pam 212- ras肿瘤细胞。另一方面，DNA结合数据表明，化合物6b和6d在双螺旋中的嵌入能力比a啶强。两种化合物都可以从几个线性双链DNA取代溴化乙锭，效率比a啶高10倍，并且在超螺旋pBR322 DNA中诱导43度解旋，而a啶仅使24度解开pBR322 DNA。总而言之，这些数据表明由化合物6b和6d在双螺旋结构中诱导的显着构象变化是由于双插入DNA结合模式所致。我们建议通
• Design, Synthesis, and Biological Properties of New Bis(acridine-4-carboxamides) as Anticancer Agents
  作者：Ippolito Antonini、Paolo Polucci、Amelia Magnano、Barbara Gatto、Manlio Palumbo、Ernesto Menta、Nicoletta Pescalli、Sante Martelli

  DOI：10.1021/jm030820x

  日期：2003.7.1

  compounds intercalate DNA; (ii). the bis derivatives with the optimal linker are considerably more DNA-affinic than corresponding monomers; (iii). overall affinity is sensitive to the nature of the linker, of the chromophores, and of the substituents at 7,7'; (iv). often, the bis derivatives show a marked AT-preferential binding. In vitro cytotoxic potency of these derivatives toward the human colon adenocarcinoma

  为了增强相应的单体4和5所显示的出色的生物学反应，两类双-啶-4-甲酰胺9在4,4'位置之间具有连接基，而13在1,1之间具有连接基。已准备好作为DNA结合和潜在的抗肿瘤剂。这些化合物的非共价DNA结合特性已使用凝胶电泳和荧光技术进行了检查。结果表明（i）。目标化合物嵌入DNA；（ii）。具有最佳接头的双衍生物比相应的单体具有更高的DNA亲和力。（iii）。总的亲和力对连接基，发色团和在7,7'处的取代基的性质敏感；（iv）。通常，双衍生物显示出明显的AT优先结合。描述了这些衍生物对人结肠腺癌细胞系（HT29）的体外细胞毒性作用，并与参考药物进行了比较。讨论了构效关系。一些高DNA亲和力和强力细胞毒性化合物9b，f和13b，c已被选为国家癌症研究所（NCI）的60种人类肿瘤细胞系的筛选对象，并被确定为抗肿瘤策略的新先导。
• Molecular design, synthesis and biological research of novel pyridyl acridones as potent DNA-binding and apoptosis-inducing agents
  作者：Bin Zhang、Kang Chen、Ning Wang、Chunmei Gao、Qinsheng Sun、Lulu Li、Yuzong Chen、Chunyan Tan、Hongxia Liu、Yuyang Jiang

  DOI：10.1016/j.ejmech.2015.02.003

  日期：2015.3

  A series of novel pyridyl acridone derivatives comprised of a pseudo-five-cyclic system to extend the pi-conjugated acridone chromophore, were designed and synthesized as potent DNA binding antitumor compounds. Most synthesized compounds displayed good activity against human leukemia K562 cells in MU tests, with compound 6d exhibiting the highest activity with IC50 value at 0.46 mu M. Moreover, 6d showed potent activities against solid tumor cell lines (0.16-3.79 mu M). Several experimental studies demonstrated that the antitumor mode of action of compound 6d involves DNA intercalation, topoisomerase I inhibition, and apoptosis induction through the mitochondrial pathway. In summary, compound 6d represents a novel and promising lead structure for the development of new potent anticancer DNA-binding agents. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Synthesis, Antitumor Cytotoxicity, and DNA-Binding of Novel <i>N-</i>5,2-Di(ω-aminoalkyl)-2,6-dihydropyrazolo[3,4,5-<i>kl</i>]acridine-5-carboxamides
  作者：Ippolito Antonini、Paolo Polucci、Amelia Magnano、Sante Martelli

  DOI：10.1021/jm010917o

  日期：2001.9.1

  A series of DNA-binding potential antitumor agents bearing a cationic carboxamide side chain attached in position peri to an electron-withdrawing atom, N-5,2-di(omega -aminoalkyl)-2,6-dihydropyrazolo[3,4,5-kl]acridine-5-carboxamides, has been prepared by reaction of the appropriate 1-chloro-9-oxo-9,10-dihyclro-4-acridinecarboxamides with the suitable (omega -aminoalkyl)-hydrazine. The noncovalent DNA-binding properties of these compounds have been examined using a fluorometric technique. In vitro cytotoxic potency of these derivatives toward the human colon adenocarcinoma cell line (HT29) is described and compared to that of reference drugs. Structure-activity relationships are discussed. Two highly DNA-affinic and potent cytotoxic compounds, 4m,o, have been identified as new leads in the antitumor strategies.