3,6,8,11,13-Pentamethyl-8H-quino[4,3,2-kl]acridinium methyl-sulphate

• 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: 3,6,8,11,13-Pentamethyl-8H-quino[4,3,2-kl]acridinium methyl-sulphate
• 英文别名: Methyl sulfate;4,8,11,16,20-pentamethyl-8-aza-20-azoniapentacyclo[11.7.1.02,7.09,21.014,19]henicosa-1(20),2(7),3,5,9,11,13(21),14(19),15,17-decaene
• 化学式: CH₃O₄S*C₂₄H₂₃N₂
• 分子量: 450.558
• InChiKey: ZLHWPZKMWRIARZ-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  4.58
• 重原子数：
  32
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  81.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1,2,6-trimethylquinolinium methosulfate 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 120.0h， 以14%的产率得到3,6,8,11,13-Pentamethyl-8H-quino[4,3,2-kl]acridinium methyl-sulphate
  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。
• N8,N13 -DISUBSTITUTED QUINO[4,3,2-KL]ACRIDINIUM SALTS AS THERAPEUTIC AGENTS
  申请人：Cancer Research Technology Limited

  公开号：EP1330456B9

  公开（公告）日：2012-01-25
• US7115619B2
  申请人：——

  公开号：US7115619B2

  公开（公告）日：2006-10-03
• Antitumor Polycyclic Acridines. 8. Synthesis and Telomerase-Inhibitory Activity of Methylated Pentacyclic Acridinium Salts
  作者：Robert A. Heald、Chetna Modi、Jenny C. Cookson、Ian Hutchinson、Charles A. Laughton、Sharon M. Gowan、Lloyd R. Kelland、Malcolm F. G. Stevens

  DOI：10.1021/jm011015q

  日期：2002.1.1

  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.