6,7-methylenedioxyquinoline-4-carboxylic acid N-[2-(piperidin-1-yl)ethyl]-N-(2-iodo-4,5-dimethoxyphenyl)amide | 791130-75-1

• 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: 6,7-methylenedioxyquinoline-4-carboxylic acid N-[2-(piperidin-1-yl)ethyl]-N-(2-iodo-4,5-dimethoxyphenyl)amide
• CAS: 791130-75-1
• 化学式: C₂₆H₂₈IN₃O₅
• 分子量: 589.43
• InChiKey: RIJHBXXEAYSDBQ-UHFFFAOYSA-N

物化性质

• 沸点：
  707.0±60.0 °C(Predicted)
• 密度：
  1.529±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.72
• 重原子数：
  35.0
• 可旋转键数：
  7.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  73.36
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  6,7-methylenedioxyquinoline-4-carboxylic acid N-[2-(piperidin-1-yl)ethyl]-N-(2-iodo-4,5-dimethoxyphenyl)amide 在 盐酸 作用下， 反应 1.5h， 以30%的产率得到16,17-Dimethoxy-20-(2-piperidin-1-ylethyl)-5,7-dioxa-11,20-diazapentacyclo[11.8.0.02,10.04,8.014,19]henicosa-1(13),2,4(8),9,11,14,16,18-octaen-21-one
  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：

  4,5-二甲氧基-2-碘苯胺 在 sodium hydride 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 6,7-methylenedioxyquinoline-4-carboxylic acid N-[2-(piperidin-1-yl)ethyl]-N-(2-iodo-4,5-dimethoxyphenyl)amide
  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

文献信息

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

  DOI：10.1016/j.bmc.2005.12.028

  日期：2006.5

  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.