8-methyl-8H-quino[4,3,2-kl]acridine | 252882-87-4

• 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-8H-quino[4,3,2-kl]acridine
• 英文别名: 8-methyl-8,20-diazapentacyclo[11.7.1.02,7.09,21.014,19]henicosa-1(20),2,4,6,9,11,13(21),14,16,18-decaene
• CAS: 252882-87-4
• 化学式: C₂₀H₁₄N₂
• 分子量: 282.345
• InChiKey: ULJIFKUWEOSDIG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  16.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  8-methyl-8H-quino[4,3,2-kl]acridine 、 碘甲烷 反应 72.0h， 以73%的产率得到8,20-Dimethyl-8-aza-20-azoniapentacyclo[11.7.1.02,7.09,21.014,19]henicosa-1(20),2,4,6,9,11,13(21),14,16,18-decaene;iodide
  参考文献：
  名称：

  Antitumor Polycyclic Acridines. 8. Synthesis and Telomerase-Inhibitory Activity of Methylated Pentacyclic Acridinium Salts

  摘要：

  Two short routes to novel methylated pentacyclic quinoacridinium salts have been devised. New compounds display telomerase-inhibitory potency (<1 muM) in the TRAP assay. 3,11-Difluoro-6,8,13-trimethyl-8H-quino[4,3,2-kl]acridinium methosulfate (12d, RHPS4, NSC 714187) has a higher selectivity for triplex and quadruplex DNA structures than the 3,6,8,11,13-pentamethyl analogue (12c, RHPS3, NSC 714186) and a low overall growth-inhibitory activity in the NCI 60 cell panel (mean GI(50) 13.18 muM); in addition, the activity profile of 12d does not COMPARE with agents of the topoisomerase II class. Compound 12d is soluble in water, stable in the pH range of 5-9, efficiently transported into tumor cells, and is currently the lead structure for further elaboration in this new class of telomerase inhibitor.

  DOI：

  10.1021/jm011015q
• 作为产物：
  描述：

  9-氯吖啶 在 sodium hydride 作用下， 以 二苯醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 8-methyl-8H-quino[4,3,2-kl]acridine
  参考文献：
  名称：

  Antitumor Polycyclic Acridines. 8. Synthesis and Telomerase-Inhibitory Activity of Methylated Pentacyclic Acridinium Salts

  摘要：

  Two short routes to novel methylated pentacyclic quinoacridinium salts have been devised. New compounds display telomerase-inhibitory potency (<1 muM) in the TRAP assay. 3,11-Difluoro-6,8,13-trimethyl-8H-quino[4,3,2-kl]acridinium methosulfate (12d, RHPS4, NSC 714187) has a higher selectivity for triplex and quadruplex DNA structures than the 3,6,8,11,13-pentamethyl analogue (12c, RHPS3, NSC 714186) and a low overall growth-inhibitory activity in the NCI 60 cell panel (mean GI(50) 13.18 muM); in addition, the activity profile of 12d does not COMPARE with agents of the topoisomerase II class. Compound 12d is soluble in water, stable in the pH range of 5-9, efficiently transported into tumor cells, and is currently the lead structure for further elaboration in this new class of telomerase inhibitor.

  DOI：

  10.1021/jm011015q

文献信息

• N8, n13 -disubstituted quino[4,3,2-kl]acridinium salts as therapeutic agents
  申请人：——

  公开号：US20040063739A1

  公开（公告）日：2004-04-01

  The present invention pertains to certain N 8 ,N 13 -disubstituted quino[4,3,2-kl]acridinium salts of formula (Q − ) which inhibit telomerase wherein: p is an integer from 0 to 4; q is an integer from 0 to 3; r is an integer from 0 to 4; each R A is —H or a ring substituent; each R B is —H or a ring substituent; each R C is —H or a ring substituent; R N8 is a nitrogen substituent; R N13 is a nitrogen substituent; and, Q is an anion. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit telomerase, to regulate cell proliferation, and in the treatment of proliferative conditions, such as cancer.

  本发明涉及某些N8，N13-二取代喹诺[4,3,2-kl]吖啶盐的化合物，其化学式为(Q−)，用于抑制端粒酶，其中：p为0至4的整数；q为0至3的整数；r为0至4的整数；每个RA为—H或环取代基；每个RB为—H或环取代基；每个RC为—H或环取代基；RN8为氮取代基；RN13为氮取代基；Q为阴离子。本发明还涉及包括这些化合物的药物组合物，以及在体外和体内使用这些化合物和组合物来抑制端粒酶，调节细胞增殖，并用于治疗增殖性疾病，如癌症。
• 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
• Antitumour polycyclic acridines. Part 10.1 Synthesis of penta- and hexa-cyclic heteroaromatic systems by radical cyclisations of substituted 9-anilinoacridines
  作者：Michael J. Ellis、Malcolm F. G. Stevens

  DOI：10.1039/b106327h

  日期：2001.11.29

  9-Anilinoacridines substituted with a bromine atom in the 2-position of the anilino group or the 1-position of the acridine moiety can be cyclised with tributyltin hydride–AIBN to penta- or hexacyclic acridines. Of the polycyclic systems 13,14-dihydropyrrolo[3′,2′,1′:8,1]quino[4,3,2-kl]acridine 14a is the most potent cytotoxic agent displaying a mean GI50 concentration against a panel of 60 human tumour

  在其2位上被溴原子取代的9-苯胺基idine啶 安尼利诺集团 或the啶部分的1位可以用 氢化三丁基锡–AIBN为五环或六环 啶。在多环体系中13,14-dihydropyrrolo [3'，2'，1'：8,1] quino [4,3,2- kl ] ac啶14a是最有效的细胞毒性剂，相对于检测组显示平均GI 50浓度0.06μM的60种人类肿瘤细胞系中
• Polycyclic fused phenanthridines: An alternative approach from benzotriazoles
  作者：Alan R. Katritzky、Weihong Du、Yasuhisa Matsukawa、Ion Ghiviriga、Sergey N. Denisenko

  DOI：10.1002/jhet.5570360417

  日期：1999.7

  We describe an alternative approach to polycyclic phenanthridines (7) and some of their analogues using conditions much milder than those previously reported. The procedure includes the generation of a benzotriazole stabilized carbanion, oxidation of the resulting anion to a radical, and elimination of nitrogen followed by ring closure to produce phenanthridines.

  我们描述了一种使用比以前报道的条件温和得多的条件的多环菲啶类化合物（7）及其某些类似物的替代方法。该方法包括生成苯并三唑稳定的碳负离子，将所得阴离子氧化为自由基，消除氮原子，然后闭环以产生菲啶。
• N8, N13 -disubstituted quino[4,3,2-kl]acridinium salts as therapeutic agents
  申请人：Cancer Research Technology Limited

  公开号：US07115619B2

  公开（公告）日：2006-10-03

  The present invention pertains to certain N8,N13-disubstituted quino[4,3,2-kl]acridinium salts of formula (Q−) which inhibit telomerase wherein: p is an integer from 0 to 4; q is an integer from 0 to 3; r is an integer from 0 to 4; each RA is —H or a ring substituent; each RB is —H or a ring substituent; each RC is —H or a ring substituent; RN8 is a nitrogen substituent; RN13 is a nitrogen substituent; and, Q is an anion. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit telomerase, to regulate cell proliferation, and in the treatment of proliferative conditions, such as cancer.

  本发明涉及某些式为（Q-）的N8，N13-二取代喹诺[4,3,2-kl]吖啶盐，其抑制端粒酶，其中：p是0到4的整数；q是0到3的整数；r是0到4的整数；每个RA是-H或环取代基；每个RB是-H或环取代基；每个RC是-H或环取代基；RN8是氮取代基；RN13是氮取代基；Q是阴离子。本发明还涉及包含这些化合物的药物组合物，以及在体内外使用这些化合物和组合物来抑制端粒酶，调节细胞增殖，并治疗增殖性疾病，如癌症。