9,10-dimethoxy-8,8-dimethyl-5,8,13,13a-tetrahydro-6H-[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinoline | 62815-56-9

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 原小檗碱生物碱及其衍生物
• 英文名称: 9,10-dimethoxy-8,8-dimethyl-5,8,13,13a-tetrahydro-6H-[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinoline
• 英文别名: 8,8-Dimethylcanadine；16,17-dimethoxy-14,14-dimethyl-5,7-dioxa-13-azapentacyclo[11.8.0.02,10.04,8.015,20]henicosa-2,4(8),9,15(20),16,18-hexaene
• CAS: 62815-56-9
• 化学式: C₂₂H₂₅NO₄
• 分子量: 367.445
• InChiKey: PKGLJWDKMKATAA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  40.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  8-methylcanadine 在 红铝 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 生成 9,10-dimethoxy-8,8-dimethyl-5,8,13,13a-tetrahydro-6H-[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinoline
  参考文献：
  名称：

  杂环化合物合成的研究。715.1用双（2-甲氧基乙氧基）氢化铝钠对顺式和反式-二联苯甲硫脲进行史蒂文斯重排。

  摘要：

  DOI：

  10.1021/jo00438a020

文献信息

• NOVEL ISOQUINOLINE DERIVATIVES
  申请人：Chen Li

  公开号：US20100286396A1

  公开（公告）日：2010-11-11

  The invention provides novel compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein R 1 to R 7 are as described herein, compositions including the compounds and methods of preparing and using the compounds.

  这项发明提供了式（I）的新化合物或其药用可接受盐，其中R1至R7如本文所述，包括这些化合物的组合物以及制备和使用这些化合物的方法。
• [EN] NOVEL ISOQUINOLINE DERIVATIVES<br/>[FR] NOUVEAUX DÉRIVÉS D'ISOQUINOLÉINE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2010128061A1

  公开（公告）日：2010-11-11

  A compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R1 to R7 have the significance given in claim 1, can be used in the form of a pharmaceutical composition.

  化合物的结构式（I）或其药学上可接受的盐，其中R1至R7具有权利要求书中给定的含义，可用作药物组合物的形式。
• Isoquinoline derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US08258149B2

  公开（公告）日：2012-09-04

  The invention provides novel compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein R1 to R7 are as described herein, compositions including the compounds and methods of preparing and using the compounds.

  本发明提供了式(I)的新化合物或其药学上可接受的盐，其中R1至R7如本文所述，包括该化合物的组合物以及制备和使用该化合物的方法。
• 8,8-Dialkyldihydroberberines with Potent Antiprotozoal Activity
  作者：Molla Endeshaw、Xiaohua Zhu、Shanshan He、Trupti Pandharkar、Emily Cason、Kiran V. Mahasenan、Hitesh Agarwal、Chenglong Li、Manoj Munde、W. David Wilson、Mark Bahar、Raymond W. Doskotch、A. Douglas Kinghorn、Marcel Kaiser、Reto Brun、Mark E. Drew、Karl A. Werbovetz

  DOI：10.1021/np300638f

  日期：2013.3.22

  Semisynthetic 8,8-dialkyldihydroberberines (8,8-DDBs) were found to possess mid- to low-nanomolar potency against Plasmodium falciparum blood-stage parasites, Leishmania donovani intracellular amastigotes, and Trypanosoma brucei brucei bloodstream forms. For example, 8,8-diethyldihydroberberine chloride (5b) exhibited in vitro IC50 values of 77, 100, and 5.3 nM against these three parasites, respectively. In turn, two 8,8-dialkylcanadines, obtained by reduction of the corresponding 8,8-DDBs, were much less potent against these parasites in vitro. While the natural product berberine is a weak DNA binder, the 8,8-DDBs displayed no affinity for DNA, as assessed by changes in the melting temperature of poly(dA.dT) DNA. Selected 8,8-DDBs showed efficacy in mouse models of visceral leishmaniasis and African trypanosomiasis, with 8,8-dimethyldihydroberberine chloride (5a) reducing liver parasitemia by 46% in L. donovani-infected BALB/c mice when given at an intraperitoneal dose of 10 mg/kg/day for five days. The 8,8-DDBs may thus serve as leads for discovering new antimalarial, antileishmanial, and antitrypanosomal drug candidates.
• US8258149B2
  申请人：——

  公开号：US8258149B2

  公开（公告）日：2012-09-04