Acetic acid 3-[(E)-3-(3-morpholin-4-yl-3-oxo-propenyl)-8-methyl-8H-quino[4,3,2-kl]acridin-6-yl]-propyl ester | 410533-80-1

• 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: Acetic acid 3-[(E)-3-(3-morpholin-4-yl-3-oxo-propenyl)-8-methyl-8H-quino[4,3,2-kl]acridin-6-yl]-propyl ester
• 英文别名: 3-[8-methyl-16-[(E)-3-morpholin-4-yl-3-oxoprop-1-enyl]-8,20-diazapentacyclo[11.7.1.02,7.09,21.014,19]henicosa-1(20),2,4,6,9,11,13(21),14(19),15,17-decaen-11-yl]propyl acetate
• CAS: 410533-80-1
• 化学式: C₃₂H₃₁N₃O₄
• 分子量: 521.616
• InChiKey: RNALPDBOKHHQHZ-ZRDIBKRKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  39
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  72
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Acetic acid 3-[(E)-3-(3-morpholin-4-yl-3-oxo-propenyl)-8-methyl-8H-quino[4,3,2-kl]acridin-6-yl]-propyl ester 、 碘甲烷 反应 48.0h， 以58%的产率得到6-(3-acetoxy-propyl)-8,13-dimethyl-3-(3-morpholin-4-yl-3-oxo-propenyl)-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：

  3-chloro-8-methyl-6-trifluoromethylsulfonyloxy-8H-quino[4,3,2-kl]acridine 在 potassium phosphate 、 tris(dibenzylideneacetone)dipalladium (0) 、 三叔丁基膦 、 9-硼双环[3.3.1]壬烷 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 69.5h， 生成 Acetic acid 3-[(E)-3-(3-morpholin-4-yl-3-oxo-propenyl)-8-methyl-8H-quino[4,3,2-kl]acridin-6-yl]-propyl ester
  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

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：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。
• N8,N13 -DISUBSTITUTED QUINO 4,3,2-KL]ACRIDINIUM SALTS AS THERAPEUTIC AGENTS
  申请人：Cancer Research Technology Limited

  公开号：EP1330456A2

  公开（公告）日：2003-07-30
• N8,N13 -DISUBSTITUTED QUINO[4,3,2-KL]ACRIDINIUM SALTS AS THERAPEUTIC AGENTS
  申请人：Cancer Research Technology Limited

  公开号：EP1330456B8

  公开（公告）日：2012-02-08
• US7115619B2
  申请人：——

  公开号：US7115619B2

  公开（公告）日：2006-10-03