5-{3-[(3-aminopropyl)(methyl)amino]propylamino}-2,10b-diaza-aceanthrylen-6-one | 166756-57-6

• 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: 5-{3-[(3-aminopropyl)(methyl)amino]propylamino}-2,10b-diaza-aceanthrylen-6-one
• 英文别名: 10-[3-[3-Aminopropyl(methyl)amino]propylamino]-1,14-diazatetracyclo[7.6.1.02,7.013,16]hexadeca-2,4,6,9,11,13(16),14-heptaen-8-one
• CAS: 166756-57-6
• 化学式: C₂₁H₂₅N₅O
• 分子量: 363.462
• InChiKey: ZEBBQFUTDQBLGT-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：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  76.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-chloro-8-hydroxy-6H-v-triazolo<4,5,1-de>acridin-6-one 、 5-{3-[(3-aminopropyl)(methyl)amino]propylamino}-2,10b-diaza-aceanthrylen-6-one 在 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 12.0h， 生成 8-hydroxy-5-<<3-acridin-5-yl)amino>propyl>amino>propyl>amino>-6H-v-triazolo<4,5,1-de>acridin-6-one
  参考文献：
  名称：

  Bisimidazoacridones and Related Compounds: New Antineoplastic Agents with High Selectivity against Colon Tumors

  摘要：

  A new class of potent and highly selective antitumor agents has been synthesized. Bisimidazoacridones, where the tetracyclic ring systems are held together by either a N-2-methyldiethylenetriamine or 3,3'-diamino-N-methyldipropylamine linker, and related asymmetrical compounds, where one of the imidazoacridone ring system was replaced by a triazoloacridone ring system, were found to be cytostatic and cytotoxic in vitro. Some of these compounds, such as 5,5'-[(methylimino)bis(3,1-propanediylimino)]bis[6H-imidazo[4,5,1-de]acridim-6-one] (4b) showed remarkably high activity and selectivity for colon cancer in the National Cancer Institute screen. This antitumor effect was also apparent in colony survival assays utilizing the colon cancer line, HCT-116, and in in vivo assays involving xenografts of tumor derived from HCT-116 in nude mice. The tested compounds exhibited relatively low acute toxicity and were well tolerated by the treated animals. The bisimidazoacridones interact with nucleic acids in vitro but preliminary experimental and modeling data indicate that in spite of their structure, they may not be bis-intercalators. While the precise mode of action of these compounds is not yet understood, they appear to be excellent candidates for clinical development.

  DOI：

  10.1021/jm00016a007
• 作为产物：
  描述：

  1-chloro-4-nitro-9,10-dihydro-9-acridinone 在 镍 盐酸 作用下， 以 二甲基亚砜 为溶剂， 反应 41.0h， 生成 5-{3-[(3-aminopropyl)(methyl)amino]propylamino}-2,10b-diaza-aceanthrylen-6-one
  参考文献：
  名称：

  Bisimidazoacridones and Related Compounds: New Antineoplastic Agents with High Selectivity against Colon Tumors

  摘要：

  A new class of potent and highly selective antitumor agents has been synthesized. Bisimidazoacridones, where the tetracyclic ring systems are held together by either a N-2-methyldiethylenetriamine or 3,3'-diamino-N-methyldipropylamine linker, and related asymmetrical compounds, where one of the imidazoacridone ring system was replaced by a triazoloacridone ring system, were found to be cytostatic and cytotoxic in vitro. Some of these compounds, such as 5,5'-[(methylimino)bis(3,1-propanediylimino)]bis[6H-imidazo[4,5,1-de]acridim-6-one] (4b) showed remarkably high activity and selectivity for colon cancer in the National Cancer Institute screen. This antitumor effect was also apparent in colony survival assays utilizing the colon cancer line, HCT-116, and in in vivo assays involving xenografts of tumor derived from HCT-116 in nude mice. The tested compounds exhibited relatively low acute toxicity and were well tolerated by the treated animals. The bisimidazoacridones interact with nucleic acids in vitro but preliminary experimental and modeling data indicate that in spite of their structure, they may not be bis-intercalators. While the precise mode of action of these compounds is not yet understood, they appear to be excellent candidates for clinical development.

  DOI：

  10.1021/jm00016a007

文献信息

• [EN] ASYMMETRIC BIS-ACRIDINES WITH ANTITUMOUR ACTIVITY AND THEIR USES<br/>[FR] BIS-ACRIDINES ASYMÉTRIQUES AYANT UNE ACTIVITÉ ANTITUMORALE ET LEURS UTILISATIONS
  申请人：POLITECHNIKA GDAŃSKA

  公开号：WO2016150799A1

  公开（公告）日：2016-09-29

  We disclose novel asymmetric bis-acridines with antitumour activity. These compounds are useful for use in pharmaceuticals, particularly in the treatment or the prevention of neoplasms.

  我们披露了具有抗肿瘤活性的新型不对称双吖啶。这些化合物可用于制药领域，特别是用于治疗或预防肿瘤。
• A New Synthetic Agent with Potent but Selective Cytotoxic Activity against Cancer
  作者：Wieslaw M. Cholody、Teresa Kosakowska-Cholody、Melinda G. Hollingshead、Humcha K. Hariprakasha、Christopher. J. Michejda

  DOI：10.1021/jm048946x

  日期：2005.6.1

  The synthesis of novel unsymmetrical bifunctional antitumor agents was accomplished by linking an imidazoacridone moiety to another polycyclic heteroaromatic moiety via linkers of various length and rigidity. These compounds bind to cellular DNA, but it is hypothesized that biological effects become manifested when the drug-DNA complexes interact with critical DNA binding proteins that are involved in repair and transcription. The most promising compound of the series, 4ad (WMC79), consists of an imidazoacridone linked to a 3-nitronaph-thalimide moiety via a 1,4-dipropanopiperazine linker. It was found to be potently, but selectively, cytotoxic against colon cancers (GI(50) = 0.5 nM, LC50 = 32 nM) and leukemias (GI(50) = 3.5 nM, LC50 = 33 nM). Compound 4ad, which appears to be a candidate for further development as an anticancer drug, kills sensitive cells by induction of apoptosis. It also showed significant in vivo activity against HCT-116 colon cancer xenografts in nude mice. Other compounds in the series also exhibited antitumor properties, but they were significantly lower than that of 4ad.
• US5508289A
  申请人：——

  公开号：US5508289A

  公开（公告）日：1996-04-16
• Bisimidazoacridones and Related Compounds: New Antineoplastic Agents with High Selectivity against Colon Tumors
  作者：Wieslaw M. Cholody、Lidia Hernandez、Lawrence Hassner、Dominic A. Scudiero、Draginja B. Djurickovic、Christopher J. Michejda

  DOI：10.1021/jm00016a007

  日期：1995.8

  A new class of potent and highly selective antitumor agents has been synthesized. Bisimidazoacridones, where the tetracyclic ring systems are held together by either a N-2-methyldiethylenetriamine or 3,3'-diamino-N-methyldipropylamine linker, and related asymmetrical compounds, where one of the imidazoacridone ring system was replaced by a triazoloacridone ring system, were found to be cytostatic and cytotoxic in vitro. Some of these compounds, such as 5,5'-[(methylimino)bis(3,1-propanediylimino)]bis[6H-imidazo[4,5,1-de]acridim-6-one] (4b) showed remarkably high activity and selectivity for colon cancer in the National Cancer Institute screen. This antitumor effect was also apparent in colony survival assays utilizing the colon cancer line, HCT-116, and in in vivo assays involving xenografts of tumor derived from HCT-116 in nude mice. The tested compounds exhibited relatively low acute toxicity and were well tolerated by the treated animals. The bisimidazoacridones interact with nucleic acids in vitro but preliminary experimental and modeling data indicate that in spite of their structure, they may not be bis-intercalators. While the precise mode of action of these compounds is not yet understood, they appear to be excellent candidates for clinical development.