8-methyl-6-methoxy-10-[(E)-(2-methoxycarbonyl)vinyl]-8H-quino[4,3,2-kl]acridine | 635682-63-2

• 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: 8-methyl-6-methoxy-10-[(E)-(2-methoxycarbonyl)vinyl]-8H-quino[4,3,2-kl]acridine
• 英文别名: (E)-3-(6-methoxy-8-methyl-8H-quino[4,3,2-kl]acridin-10-yl)acrylic acid methyl ester；methyl (E)-3-(11-methoxy-8-methyl-8,20-diazapentacyclo[11.7.1.02,7.09,21.014,19]henicosa-1(20),2(7),3,5,9,11,13(21),14,16,18-decaen-5-yl)prop-2-enoate
• CAS: 635682-63-2
• 化学式: C₂₅H₂₀N₂O₃
• 分子量: 396.445
• InChiKey: VLFWAIGKYMVYIM-PKNBQFBNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  51.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  8-methyl-6-methoxy-10-[(E)-(2-methoxycarbonyl)vinyl]-8H-quino[4,3,2-kl]acridine 、 碘甲烷 反应 48.0h， 以38%的产率得到6-Methoxy-10-((E)-2-methoxycarbonyl-vinyl)-8,13-dimethyl-8H-8-aza-13-azonia-dibenzo[a,de]anthracen; iodide
  参考文献：
  名称：

  Antitumor Polycyclic Acridines. 17. Synthesis and Pharmaceutical Profiles of Pentacyclic Acridinium Salts Designed To Destabilize Telomeric Integrity

  摘要：

  Palladium(O)-mediated Suzuki-Miyaura and Heck transformations have been exploited to provide examples of 8-methylquino[4,3,2-kl]acridines and 8,13-dimethylquino[4,3,2-kl]acridinium iodides bearing bulky saturated (3-acetoxy)propyl or (E)-3-(morpholin-4-yl)-3-oxopropenyl substituents variously in the 3-, 6-, or 10-positions of the pentacyclic nucleus. The pharmacological/pharmaceutical properties of four compounds (4, RHPS4), (5, IH383), (6, RHPS16), and (17, RHPS19) were measured to assess their clinical potential as DNA G-quadruplex-stabilizing/telomerase inhibitory agents. The following properties were measured: stability in tissue culture media in the presence of A549 lung and MCF-7 breast tumor cells, metabolic stability when incubated with rat liver microsomes, and rate of uptake and subcellular location in A549 and MCF-7 cells. Compound 17 was unstable in tissue culture media, failed to achieve nuclear access, and was excluded from further consideration. Of the other agents, 4 exhibited the most favorable pharmaceutical profile: the agent has appropriate stability in the presence of tumor cells and rat liver microsomes and achieves rapid ingress into cell nuclei where the putative molecular target is located.

  DOI：

  10.1021/jm058031y
• 作为产物：
  描述：

  6-chloro-1-hydroxy-3-methoxy-10-methylacridin-9(10H)-one 在 四(三苯基膦)钯 、 tris(dibenzylideneacetone)dipalladium (0) potassium phosphate 、 三叔丁基膦 、 碳酸氢钠 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 乙二醇二甲醚 、 二氯甲烷 为溶剂， 反应 48.33h， 生成 8-methyl-6-methoxy-10-[(E)-(2-methoxycarbonyl)vinyl]-8H-quino[4,3,2-kl]acridine
  参考文献：
  名称：

  抗肿瘤多环a啶。钯（0）介导的带有外围取代基的喹[4,3,2-kl] r啶的合成作为潜在的端粒维持抑制剂。

  摘要：

  在1-位上带有溴或三氟甲基磺酰氧基取代基的取代的2-（新戊酰氨基）苯硼酸和3,6-二取代的-10-甲基ac啶酮13之间的Pd（0）介导的偶联产生可被环化成的中间体1-芳基rid啶酮16新的8-甲基喹[4,3,2-kl] ac啶17与氯氧化磷或6 M HCl的乙醇溶液。用三氟甲磺酸酯取代的底物17和丙烯酸衍生物之间的heck反应得到在6-位具有不饱和侧链的喹诺啶啶。由9-硼环[3,3,1]壬烷（9-BBN）与乙酸烯丙酯或N-烯丙基三氟乙酰胺相互作用制得的炔烷参加了Suzuki-Miyaura反应，与氯取代的8-甲基喹诺啶啶形成带有官能化丙基的衍生物在6位和10位

  DOI：

  10.1039/b305177n

文献信息

• Antitumour polycyclic acridines. Palladium(<scp>0</scp>) mediated syntheses of quino[4,3,2-kl]acridines bearing peripheral substituents as potential telomere maintenance inhibitors
  作者：Robert A. Heald、Malcolm F. G. Stevens

  DOI：10.1039/b305177n

  日期：——

  triflate-substituted substrates 17 and acrylic acid derivatives afforded quinoacridines with unsaturated side-chains in the 6-position. Alkylboranes, prepared by interaction of 9-borabicyclo[3,3,1]nonane (9-BBN) and allyl acetate or N-allyltrifluoroacetamide, participated in Suzuki-Miyaura reactions with chloro-substituted 8-methylquinoacridines to form derivatives bearing functionalised propyl groups in the

  在1-位上带有溴或三氟甲基磺酰氧基取代基的取代的2-（新戊酰氨基）苯硼酸和3,6-二取代的-10-甲基ac啶酮13之间的Pd（0）介导的偶联产生可被环化成的中间体1-芳基rid啶酮16新的8-甲基喹[4,3,2-kl] ac啶17与氯氧化磷或6 M HCl的乙醇溶液。用三氟甲磺酸酯取代的底物17和丙烯酸衍生物之间的heck反应得到在6-位具有不饱和侧链的喹诺啶啶。由9-硼环[3,3,1]壬烷（9-BBN）与乙酸烯丙酯或N-烯丙基三氟乙酰胺相互作用制得的炔烷参加了Suzuki-Miyaura反应，与氯取代的8-甲基喹诺啶啶形成带有官能化丙基的衍生物在6位和10位
• Antitumor Polycyclic Acridines. 17. Synthesis and Pharmaceutical Profiles of Pentacyclic Acridinium Salts Designed To Destabilize Telomeric Integrity
  作者：Jennifer C. Cookson、Robert A. Heald、Malcolm F. G. Stevens

  DOI：10.1021/jm058031y

  日期：2005.11.1

  Palladium(O)-mediated Suzuki-Miyaura and Heck transformations have been exploited to provide examples of 8-methylquino[4,3,2-kl]acridines and 8,13-dimethylquino[4,3,2-kl]acridinium iodides bearing bulky saturated (3-acetoxy)propyl or (E)-3-(morpholin-4-yl)-3-oxopropenyl substituents variously in the 3-, 6-, or 10-positions of the pentacyclic nucleus. The pharmacological/pharmaceutical properties of four compounds (4, RHPS4), (5, IH383), (6, RHPS16), and (17, RHPS19) were measured to assess their clinical potential as DNA G-quadruplex-stabilizing/telomerase inhibitory agents. The following properties were measured: stability in tissue culture media in the presence of A549 lung and MCF-7 breast tumor cells, metabolic stability when incubated with rat liver microsomes, and rate of uptake and subcellular location in A549 and MCF-7 cells. Compound 17 was unstable in tissue culture media, failed to achieve nuclear access, and was excluded from further consideration. Of the other agents, 4 exhibited the most favorable pharmaceutical profile: the agent has appropriate stability in the presence of tumor cells and rat liver microsomes and achieves rapid ingress into cell nuclei where the putative molecular target is located.