1,4-dimethoxy-8,9-methylenedioxy-11H-indeno[1,2-c]isoquinoline hydrochloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 1,4-dimethoxy-8,9-methylenedioxy-11H-indeno[1,2-c]isoquinoline hydrochloride
• 英文别名: 14,17-Dimethoxy-5,7-dioxa-20-azoniapentacyclo[10.8.0.02,10.04,8.013,18]icosa-1(12),2,4(8),9,13,15,17,19-octaene;chloride
• 化学式: C₁₉H₁₅NO₄*ClH
• 分子量: 357.793
• InChiKey: ZURIWWOSNUKPSV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.97
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,5-二甲氧基苯甲醛 在 盐酸 、 sodium tetrahydroborate 、 magnesium sulfate 作用下， 以 乙醇 、 氯仿 、 水 为溶剂， 反应 30.0h， 生成 1,4-dimethoxy-8,9-methylenedioxy-11H-indeno[1,2-c]isoquinoline hydrochloride
  参考文献：
  名称：

  Synthesis of Indenoisoquinoliniums and Methods of Use

  摘要：

  描述了取代的茚喹啉化合物，以及取代的茚喹啉化合物的制药配方。还描述了制备取代的茚喹啉化合物的方法。还描述了使用所述的取代的茚喹啉化合物或其制药配方来治疗哺乳动物癌症的方法。

  公开号：

  US20080242692A1

文献信息

• Synthesis of Indenoisoquinoliniums and Methods of Use
  申请人：Cushman Mark S.

  公开号：US20080242692A1

  公开（公告）日：2008-10-02

  Substituted indenoisoquinolinium compounds, and pharmaceutical formulations of substituted indenoisoquinolinium compounds are described. Also described are processes for preparing substituted indenoisoquinolinium compounds. Also described are methods for treating cancer in mammals using the described substituted indenoisoquinolinium compounds or pharmaceutical formulations thereof.

  描述了取代的茚喹啉化合物，以及取代的茚喹啉化合物的制药配方。还描述了制备取代的茚喹啉化合物的方法。还描述了使用所述的取代的茚喹啉化合物或其制药配方来治疗哺乳动物癌症的方法。
• SYNTHESIS OF INDENOISOQUINOLINIUMS AND METHODS OF USE
  申请人：Purdue Research Foundation

  公开号：EP1735281A2

  公开（公告）日：2006-12-27
• US7781445B2
  申请人：——

  公开号：US7781445B2

  公开（公告）日：2010-08-24
• [EN] SYNTHESIS OF INDENOISOQUINOLINIUMS AND METHODS OF USE<br/>[FR] SYNTHESE D'INDENOISOQUINOLINIUMS ET TECHNIQUES D'UTILISATION
  申请人：CUSHMAN MARK S

  公开号：WO2005089294A2

  公开（公告）日：2005-09-29

  Substituted indenoisoquinolinium compounds, and pharmaceutical formulations of substituted indenoisoquinolinium compounds are described. Also described are processes for preparing substituted indenoisoquinolinium compounds. Also described are methods for treating cancer in mammals using the described substituted indenoisoquinolinium compounds or pharmaceutical formulations thereof.
• Synthesis and Mechanism of Action Studies of a Series of Norindenoisoquinoline Topoisomerase I Poisons Reveal an Inhibitor with a Flipped Orientation in the Ternary DNA−Enzyme−Inhibitor Complex As Determined by X-ray Crystallographic Analysis
  作者：Alexandra Ioanoviciu、Smitha Antony、Yves Pommier、Bart L. Staker、Lance Stewart、Mark Cushman

  DOI：10.1021/jm050076b

  日期：2005.7.1

  Several norindenoisoquinolines substituted with methoxy or methylenedioxy groups have been prepared and their anticancer properties evaluated in cancer cell cultures and in topoisomerase I inhibition assays. 2,3-Dimethoxy-8,9-methylenedioxy-11H-indeno[1,2-c]isoquinoline hydrochloride (14) is a strong topoisomerase I inhibitor and also displays very high cytotoxicity in the NCI cancer cell culture screen (mean graph midpoint of 50 nM). The X-ray crystal structure of norindenoisoquinoline 14 in complex with topoisomerase I and DNA has been solved, providing insight into the structure-activity relationships within this class of new anticancer agents. The number and position of the norindenoisoquinoline substituents have a significant influence on biological activity and demonstrate that substitution on the nitrogen atom is not an absolute requirement for the antitumor effect of the indenoisoquinolines. Removal of the 11-keto group from the lead compound 1 and replacement of the N-alkyllactam with an unsubstituted pyridine ring causes the indenoisoquinoline ring system to flip over in the DNA-enzyme-inhibitor ternary complex. This allows the nitrogen atom to assume the hydrogen bond acceptor role of the 11-keto group, resulting in hydrogen bonding to Arg364.