Ethyl 16,17-dimethoxy-5,7-dioxa-11-azapentacyclo[11.8.0.02,10.04,8.014,19]henicosa-1(21),2,4(8),9,11,13,15,17,19-nonaene-20-carboxylate | 693263-04-6

• 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: Ethyl 16,17-dimethoxy-5,7-dioxa-11-azapentacyclo[11.8.0.02,10.04,8.014,19]henicosa-1(21),2,4(8),9,11,13,15,17,19-nonaene-20-carboxylate
• CAS: 693263-04-6
• 化学式: C₂₃H₁₉NO₆
• 分子量: 405.407
• InChiKey: YMYIYTVJUDJNTI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  76.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Ethyl 16,17-dimethoxy-5,7-dioxa-11-azapentacyclo[11.8.0.02,10.04,8.014,19]henicosa-1(21),2,4(8),9,11,13,15,17,19-nonaene-20-carboxylate 在 sodium hydroxide 、 氯化亚砜 作用下， 以 乙醇 为溶剂， 生成 2,3-Dimethoxy-8,10-dioxa-6-aza-cyclopenta[b]chrysene-13-carboxylic acid 3-dimethylamino-propyl ester
  参考文献：
  名称：

  Dimethoxybenzo[i]phenanthridine-12-carboxylic acid derivatives and 6H-dibenzo[c,h][2,6]naphthyridin-5-ones with potent topoisomerase I-targeting activity and cytotoxicity

  摘要：

  The exceptional TOP1-targeting activity and antitumor activity of ARC-111, 1, prompted studies on similarly substituted benzo[i]phenanthridine-12-carboxylic ester and amide derivatives. These studies were extended to include 6-substituted 8,9-dimethoxy-2,3-methylenedioxy-dibenzo [c,h] [2,6]naphthyridin-5-ones, which represent reversed lactam analogues of 1. Several of these analogues retained the potent TOP1-targeting activity and cytotoxicity observed for ARG-111. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.08.070
• 作为产物：
  描述：

  3-(6,7-methylenedioxyquinolin-4-yl)-2-(2-iodo-4,5-dimethoxyphenyl)acrylic acid ethyl ester 以 乙腈 为溶剂， 反应 0.75h， 以51%的产率得到Ethyl 16,17-dimethoxy-5,7-dioxa-11-azapentacyclo[11.8.0.02,10.04,8.014,19]henicosa-1(21),2,4(8),9,11,13,15,17,19-nonaene-20-carboxylate
  参考文献：
  名称：

  2,3-二甲氧基-8,9-亚甲基二氧基-苯并[i]菲啶-12-羧酸的酯和酰胺：有效的细胞毒性和拓扑异构酶I靶向剂。

  摘要：

  5-（2-N，N-二甲基氨基）乙基-8,9-二甲氧基-2,3-亚甲基二氧基-5H-二苯并[c，h] [1,6]萘啶的异常拓扑异构酶I靶向活性和抗肿瘤活性-6-一（ARC-111，topovale）促进了对类似取代的苯并[i]菲啶-12-羧酸酯和酰胺衍生物的研究。在所评估的苯并[i]菲啶-12-羧酸酯中，2-（N，N-二甲基氨基）乙基，2-（N，N-二甲基氨基）-1-甲基乙基和2-（N，N-二甲基氨基） -1,1-二甲基乙基酯在RPMI8402和KB3-1细胞中具有相似的细胞毒性，范围从30到55 nM。几种羧酰胺衍生物具有有效的拓扑异构酶I靶向活性和细胞毒性。2-（N，N-二甲基氨基）乙基，2-（N，N-二乙基氨基）乙基和2-（吡咯烷基-1-基）乙基酰胺是更具细胞毒性的苯并[i]菲啶-12-羧酸衍生物，

  DOI：

  10.1016/j.bmc.2005.07.033

文献信息

• [EN] METHYLENEDIOXYBENZO [I] PHENANTHRIDINE DERIVATIVES USED TO TREAT CANCER<br/>[FR] DÉRIVÉS DE MÉTHYLÈNEDIOXYBENZO [I] PHÉNANTHRIDINE POUR TRAITER LE CANCER
  申请人：UNIV RUTGERS

  公开号：WO2010102219A1

  公开（公告）日：2010-09-10

  The invention provides compounds of formula I: wherein A, B, X, and Y have any of the values defined in the specification, as well as pharmaceutical compositions comprising such compounds, processes for preparing such compounds, and therapeutic methods for treating cancer and other topoisomerase mediated conditions.

  该发明提供了具有以下结构的化合物：其中A、B、X和Y具有规范中定义的任何值，以及包含这些化合物的药物组合物，制备这些化合物的方法，以及治疗癌症和其他拓扑异构酶介导疾病的治疗方法。
• 12-Substituted 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridines as novel topoisomerase I-targeting antitumor agents
  作者：Wei Feng、Mavurapu Satyanarayana、Yuan-Chin Tsai、Angela A. Liu、Leroy F. Liu、Edmond J. LaVoie

  DOI：10.1016/j.bmc.2009.02.023

  日期：2009.4

  influence of a hydroxymethyl, formyl, N,N-dimethylaminomethyl, 2-(N,N-dimethylamino)ethyl, 3-(N,N-dimethylamino)propyl), and 4-(N,N-dimethylamino)butyl substituent at the 12-position on TOP1-targeting activity and tumor cell growth was evaluated. In addition, the relative pharmacologic activities of the 12-carboxamide analog, as well as its N-methyl and N,N-dimethyl derivatives were assessed.

  2,3-二甲氧基-8,9-亚甲二氧基苯并[ i ]菲啶及其一些 12-取代类似物作为 TOP1 靶向剂具有活性。进行研究以进一步评估该系列非喜树碱 TOP1 靶向药物的潜力。羟甲基、甲酰基、N , N-二甲基氨基甲基、2-( N , N-二甲基氨基)乙基、3-( N , N-二甲基氨基)丙基)和4-( N , N-二甲基氨基)丁基取代基的影响评估了 TOP1 靶向活性和肿瘤细胞生长的 12 位。此外，还评估了12-甲酰胺类似物及其N-甲基和N , N-二甲基衍生物的相对药理活性。
• Topoisomerase-targeting agents
  申请人：LaVoie J. Edmond

  公开号：US20060004008A1

  公开（公告）日：2006-01-05

  The invention provides compounds of formula I or formula II: wherein: the bond represented by — is a single bond or a double bond, and R 1 -R 5 , X, and Y have any of the meanings defined in the specification and their pharmaceutically acceptable salts. The invention also provides pharmaceutical compositions comprising a compound of formula I or II, processes for preparing compounds of formula I or II, intermediates useful for preparing compounds of formula I or II, and therapeutic methods for treating cancer and other topoisomerase related conditions using compounds of formula I or II.

  本发明提供了公式I或公式II的化合物：其中：由—表示的键是单键或双键，R1-R5，X和Y具有规范中定义的任何含义及其药学上可接受的盐。本发明还提供了包含公式I或II化合物的制药组合物，制备公式I或II化合物的方法，用于制备公式I或II化合物的中间体，以及使用公式I或II化合物治疗癌症和其他拓扑异构酶相关疾病的治疗方法。
• Methylenedioxybenzo [I] phenanthridine derivatives used to treat cancer
  申请人：Rutgers, The State University of New Jersey

  公开号：US10179789B2

  公开（公告）日：2019-01-15

  The invention provides compounds of formula I: wherein A, B, X, and Y have any of the values defined in the specification, as well as pharmaceutical compositions comprising such compounds, processes for preparing such compounds, and therapeutic methods for treating cancer and other topoisomerase mediated conditions.

  本发明提供了式 I 的化合物： 其中A、B、X和Y具有说明书中定义的任何值，以及包含此类化合物的药物组合物、制备此类化合物的工艺和治疗癌症及其他拓扑异构酶介导的病症的治疗方法。
• TOPOISOMERASE-TARGETING AGENTS
  申请人：LaVoie Edmond J.

  公开号：US20090258890A1

  公开（公告）日：2009-10-15

  The invention provides compounds of formula I or formula II: wherein: the bond represented by is a single bond or a double bond, and R 1 -R 5 , X, and Y have any of the meanings defined in the specification and their pharmaceutically acceptable salts. The invention also provides pharmaceutical compositions comprising a compound of formula I or II, processes for preparing compounds of formula I or II, intermediates useful for preparing compounds of formula I or II, and therapeutic methods for treating cancer and other topoisomerase related conditions using compounds of formula I or II.