5-chloro-8-hydroxy-6H-v-triazolo<4,5,1-de>acridin-6-one | 128113-28-0

• 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-chloro-8-hydroxy-6H-v-triazolo<4,5,1-de>acridin-6-one
• 英文别名: 5-chloro-8-hydroxy-6H-ν-triazolo<4,5,1-de>acridin-6-one；5-chloro-8-hydroxy-6H-[1,2,3]-triazolo[4,5,l-de]acridin-6-one；10-chloro-5-hydroxy-1,14,15-triazatetracyclo[7.6.1.02,7.013,16]hexadeca-2(7),3,5,9,11,13(16),14-heptaen-8-one
• CAS: 128113-28-0
• 化学式: C₁₃H₆ClN₃O₂
• 分子量: 271.663
• InChiKey: AXCJXJWHTQKTGC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.19
• 重原子数：
  19.0
• 可旋转键数：
  0.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  67.49
• 氢给体数：
  1.0
• 氢受体数：
  5.0

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：

  8-氯-5-硝基-吖啶-2,9-二醇 在 盐酸 、 tin(ll) chloride 、 sodium nitrite 作用下， 生成 5-chloro-8-hydroxy-6H-v-triazolo<4,5,1-de>acridin-6-one
  参考文献：
  名称：

  新的不对称双ac啶衍生物对人实体瘤，特别是胰腺癌的设计，合成和高抗肿瘤潜力及其稳定DNA G-四链体的独特能力。

  摘要：

  已经开发了新的有前途的不对称双ac啶衍生物（UAs）。通过使4-硝基或4-甲基ac啶酮，咪唑ac啶酮和三唑并ac啶酮衍生物与通过氨基烷基链连接的1-硝基ac啶化合物缩合，合成包括36种化合物的三类化合物。细胞毒性筛选揭示了这些化合物对几种肿瘤细胞系的高效力。特别地，咪唑并rid啶酮-1-硝基ac啶二聚体强烈抑制胰腺Panc-1，Mia-Pa-Ca-2，Capan-2和前列腺癌DU-145细胞的生长。所研究的化合物对Walker 256大鼠腺癌显示出非常强的抗肿瘤活性（T / C> 300％）。针对裸鼠中的12种人类肿瘤异种移植物测试了所选的26种UA，包括结肠癌，乳腺癌，前列腺癌和胰腺癌。对分子作用机理的研究表明，这些不对称的二聚体对G-四链体的存在做出了显着的响应，而不是对dsDNA的响应。UAs对G-四链体稳定的效能与结构-活性的关系表明，这种药物-G-四链体复合物的热稳定性不仅取决于

  DOI：

  10.1016/j.ejmech.2020.112599

文献信息

• 8-Substituted 5-[(aminoalkyl)amino]-6H-v-triazolo[4,5,1-de]acridin-6-ones as potential antineoplastic agents. Synthesis and biological activity
  作者：Wieslaw M. Cholody、Sante Martelli、Jerzy Konopa

  DOI：10.1021/jm00172a028

  日期：1990.10

  A series of 8-substituted 5-[(aminoalkyl)amino]-6H-v-triazolo[4,5,1-de]acridin-6-ones (2), structurally related to the imidazoacridinones (1), was synthesized and tested for cytotoxic and antineoplastic activity. Preliminary biological results indicated that the 8-OH derivatives possess the highest antitumor activity. No relationship has been found between the nature of the C-8 substituent and antitumor

  合成了一系列与咪唑并rid啶酮（1）结构相关的一系列8-取代的5-[（氨基烷基）氨基] -6H-v-三唑并[4,5,1-de] ac啶-6-（2），并测试细胞毒性和抗肿瘤活性。初步的生物学结果表明，8-OH衍生物具有最高的抗肿瘤活性。在C-8取代基的性质和抗肿瘤活性之间未发现任何关系。
• The Effect of Conjugation with Octaarginine, a Cell-Penetrating Peptide on Antifungal Activity of Imidazoacridinone Derivative
  作者：Kamila Rząd、Ewa Paluszkiewicz、Damian Neubauer、Mateusz Olszewski、Katarzyna Kozłowska-Tylingo、Wojciech Kamysz、Iwona Gabriel

  DOI：10.3390/ijms222413190

  日期：——

  index value of the conjugate for human pathogenic strains remained favourable and no hemolytic activity was observed. The inhibitory effect of the analysed compound on yeast topoisomerase II activity suggested its molecular target. In summary, conjugation with R8 effectively increased imidazoacridinone derivative ability to enter the fungal cell and achieve a concentration inside the cell that resulted

  吖啶细胞穿透肽缀合物是抗肿瘤化学疗法中极其重要的化合物家族。尽管生物活性肽可以用作纳米载体来走私抗菌化合物，但这些缀合物在抗菌治疗中并未得到如此广泛的分析。我们合成的咪唑吖啶酮衍生物（化合物1-R8 ）的八精氨酸缀合物对参考和耐氟康唑临床菌株表现出高抗真菌活性（MIC ≤ 4 μg mL -1）。我们的结果清楚地证明了母体化合物和化合物1-R8积累的质量差异结合成真菌细胞。只有后者被有效运输和积累。显微镜和流式细胞术分析提供了一些证据，表明化合物1-R8的杀伤活性可能与真菌细胞膜通透性的变化有关。该偶联物对人胚肾 (HEK-293) 和人肝 (HEPG2) 癌细胞系表现出低细胞毒性。尽管如此，缀合物对人类致病菌株的选择性指数值仍然良好，并且没有观察到溶血活性。分析的化合物对酵母拓扑异构酶 II 活性的抑制作用表明其分子靶点。总之，与R8共轭有效提高咪唑吖啶酮衍生物进入真菌细胞的能力，并在细
• CHOLODY, WIESLAW M.;MARTELLI, SANTE;KONOPA, JERZY, J. MED. CHEM, 33,(1990) N0, C. 2852-2856
  作者：CHOLODY, WIESLAW M.、MARTELLI, SANTE、KONOPA, JERZY

  DOI：——

  日期：——