4-methyl-6,7-methylenedioxyquinoline | 51048-62-5

• 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: 4-methyl-6,7-methylenedioxyquinoline
• 英文别名: 8-Methyl-[1,3]dioxolo[4,5-g]quinoline
• CAS: 51048-62-5
• 化学式: C₁₁H₉NO₂
• 分子量: 187.198
• InChiKey: KEQPMCOPCNPVHY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  31.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-methyl-6,7-methylenedioxyquinoline 在 四(三苯基膦)钯 吡啶 、 potassium permanganate 、 selenium(IV) oxide 、 氯化亚砜 、 sodium hydride 、 三乙胺 、 silver carbonate 、 sodium iodide 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.5h， 生成 13-(2-Dibenzylamino-ethyl)-2,3-dimethoxy-13H-8,10-dioxa-6,13-diaza-cyclopenta[b]chrysen-12-one
  参考文献：
  名称：

  6-Substituted 6H-dibenzo[c,h][2,6]naphthyridin-5-ones: Reversed lactam analogues of ARC-111 with potent topoisomerase I-targeting activity and cytotoxicity

  摘要：

  6-substituted 8,9-dimethoxy-2,3-methylenedioxy-6H-dibenzo[c,h][2,6]naphtyridin-5-ones were synthesized and evaluated for topoisomerase I-targeting activity and cytotoxicity. Several of these reversed lactam analogues of ARC-111 exhibited exceptional cytotoxicity with IC50 values ranging from 0.5 to 3.0 nM. In contrast to topotecan, no resistance was observed with several of these reversed lactam analogues in tumor cell lines that overexpressed the efflux transporters MDR1 or BCRP. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.12.028
• 作为产物：
  描述：

  丁烯酮 在 iron(III) chloride 、 溶剂黄146 作用下， 反应 1.58h， 以44%的产率得到4-methyl-6,7-methylenedioxyquinoline
  参考文献：
  名称：

  Topoisomerase-targeting agents

  摘要：

  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。

  公开号：

  US20060004008A1

文献信息

• Esters and amides of 2,3-dimethoxy-8,9-methylenedioxy-benzo[i]phenanthridine-12-carboxylic acid: Potent cytotoxic and topoisomerase I-targeting agents
  作者：Shejin Zhu、Alexander L. Ruchelman、Nai Zhou、Angela A. Liu、Leroy F. Liu、Edmond J. LaVoie

  DOI：10.1016/j.bmc.2005.07.033

  日期：2005.12

  N-dimethylamino)ethyl-8,9-dimethoxy-2,3-methylenedioxy-5H-dibenzo[c,h][1,6 ]naphthyridin-6-one (ARC-111, topovale) prompted studies on similarly substituted benzo[i]phenanthridine-12-carboxylic ester and amide derivatives. Among the benzo[i]phenanthridine-12-carboxylic esters evaluated, the 2-(N,N-dimethylamino)ethyl, 2-(N,N-dimethylamino)-1-methylethyl, and 2-(N,N-dimethylamino)-1,1-dimethylethyl esters

  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，
• 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
  作者：Alexander L. Ruchelman、Shejin Zhu、Nai Zhou、Angela Liu、Leroy F. Liu、Edmond J. LaVoie

  DOI：10.1016/j.bmcl.2004.08.070

  日期：2004.11

  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.
• 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.
• SOLUBILIZED TOPOISOMERASE POISON AGENTS
  申请人：LaVoie Edmond J.

  公开号：US20100240664A1

  公开（公告）日：2010-09-23

  The invention provides compounds of formula I: wherein A, B, W, Y, Z, and R 1 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, processes for preparing compounds of formula I, intermediates useful for preparing compounds of formula I, and therapeutic methods for treating cancer using compounds of formula I.
• US7208492B2
  申请人：——

  公开号：US7208492B2

  公开（公告）日：2007-04-24