N-(2-methylthiophene)-10-azaartemisinin

• 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: N-(2-methylthiophene)-10-azaartemisinin
• 英文别名: (1R,4S,5R,8S,9R,12R,13R)-1,5,9-trimethyl-11-(thiophen-2-ylmethyl)-14,15,16-trioxa-11-azatetracyclo[10.3.1.04,13.08,13]hexadecan-10-one
• 化学式: C₂₀H₂₇NO₄S
• 分子量: 377.505
• InChiKey: IBSYINNTJVYECS-QGKRQCMOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  76.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-噻吩甲胺 、 青蒿素 在 2,6-二叔丁基-4-甲基苯酚 、 硫酸 、 silica gel 作用下， 生成 N-(2-methylthiophene)-10-azaartemisinin
  参考文献：
  名称：

  Syntheses and Antimalarial Activities of N-Substituted 11-Azaartemisinins

  摘要：

  A two-step reaction sequence between artemisinin and methanolic ammonia followed by treatment with Amberlyst 15 yielded 11-azaartemisinin in 65% yield. Substituting a variety of primary alkyl- and heteroaromatic amines for ammonia in the reaction sequence yields N-substituted 11-azaartemisinins in similar or greater yield. When Amberlyst 15 is replaced by a mixture of sulfuric acid/silica gel, both 11-azaartemisinin and the expected metabolite, 10-azadesoxyartemisinin, are formed in 45% and 15% yields, respectively. In vitro and in vivo test data for a number of novel N-substituted 11-azaartemisinins, against drug-resistant strains of Plasmodium falciparum, show they possess antimalarial activities equal to or greater than that of artemisinin. The most active derivative, N-(2'-acetaldehydo)-11-azaartemisinin, 17, was 26 times more active in vitro and 4 times more active in vivo than artemisinin.

  DOI：

  10.1021/jm00026a012

文献信息

• Syntheses and Antimalarial Activities of N-Substituted 11-Azaartemisinins
  作者：Daniel S. Torok、Herman Ziffer、Steven R. Meshnick、Xing-Qing Pan、Arba Ager

  DOI：10.1021/jm00026a012

  日期：1995.12

  A two-step reaction sequence between artemisinin and methanolic ammonia followed by treatment with Amberlyst 15 yielded 11-azaartemisinin in 65% yield. Substituting a variety of primary alkyl- and heteroaromatic amines for ammonia in the reaction sequence yields N-substituted 11-azaartemisinins in similar or greater yield. When Amberlyst 15 is replaced by a mixture of sulfuric acid/silica gel, both 11-azaartemisinin and the expected metabolite, 10-azadesoxyartemisinin, are formed in 45% and 15% yields, respectively. In vitro and in vivo test data for a number of novel N-substituted 11-azaartemisinins, against drug-resistant strains of Plasmodium falciparum, show they possess antimalarial activities equal to or greater than that of artemisinin. The most active derivative, N-(2'-acetaldehydo)-11-azaartemisinin, 17, was 26 times more active in vitro and 4 times more active in vivo than artemisinin.