(E)-3,7-dimethyl-N-(2-(((1S,2R,4S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)oxy)ethyl)octa-2,6-dien-1-amine | 1588776-68-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (E)-3,7-dimethyl-N-(2-(((1S,2R,4S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)oxy)ethyl)octa-2,6-dien-1-amine
• 英文别名: (2E)-3,7-dimethyl-N-[2-[[(1S,2R,4S)-1,7,7-trimethyl-2-bicyclo[2.2.1]heptanyl]oxy]ethyl]octa-2,6-dien-1-amine
• CAS: 1588776-68-4
• 化学式: C₂₂H₃₉NO
• 分子量: 333.558
• InChiKey: XJZQWBNCSAHKPP-AIBDDGKSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  甲烷磺酸 、 (E)-3,7-dimethyl-N-(2-(((1S,2R,4S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)oxy)ethyl)octa-2,6-dien-1-amine 以 二氯甲烷 为溶剂， 以64%的产率得到(E)-N-(2-((1r,3r,5r,7r)-adamantan-2-yloxy)ethyl)-3,7-dimethylocta-2,6-dien-1-amine mesylate
  参考文献：
  名称：

  Multitarget Drug Discovery for Tuberculosis and Other Infectious Diseases

  摘要：

  We report the discovery of a series of new drug leads that have potent activity against Mycobacterium tuberculosis as well as against other bacteria, fungi, and a malaria parasite. The compounds are analogues of the new tuberculosis (TB) drug SQ109 (1), which has been reported to act by inhibiting a transporter called MmpL3, involved in cell wall biosynthesis. We show that 1 and the new compounds also target enzymes involved in menaquinone biosynthesis and electron transport, inhibiting respiration and ATP biosynthesis, and are uncouplers, collapsing the pH gradient and membrane potential used to power transporters. The result of such multitarget inhibition is potent inhibition of TB cell growth, as well as very low rates of spontaneous drug resistance. Several targets are absent in humans but are present in other bacteria, as well as in malaria parasites, whose growth is also inhibited.

  DOI：

  10.1021/jm500131s
• 作为产物：
  描述：

  N-((E)-3,7-dimethylocta-2,6-dien-1-yl)-2-(((1S,2R,4S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)oxy)acetamide 在 lithium aluminium tetrahydride 、 ammonium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 10.33h， 以65%的产率得到(E)-3,7-dimethyl-N-(2-(((1S,2R,4S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)oxy)ethyl)octa-2,6-dien-1-amine
  参考文献：
  名称：

  Multitarget Drug Discovery for Tuberculosis and Other Infectious Diseases

  摘要：

  We report the discovery of a series of new drug leads that have potent activity against Mycobacterium tuberculosis as well as against other bacteria, fungi, and a malaria parasite. The compounds are analogues of the new tuberculosis (TB) drug SQ109 (1), which has been reported to act by inhibiting a transporter called MmpL3, involved in cell wall biosynthesis. We show that 1 and the new compounds also target enzymes involved in menaquinone biosynthesis and electron transport, inhibiting respiration and ATP biosynthesis, and are uncouplers, collapsing the pH gradient and membrane potential used to power transporters. The result of such multitarget inhibition is potent inhibition of TB cell growth, as well as very low rates of spontaneous drug resistance. Several targets are absent in humans but are present in other bacteria, as well as in malaria parasites, whose growth is also inhibited.

  DOI：

  10.1021/jm500131s

文献信息

• Multitarget Drug Discovery for Tuberculosis and Other Infectious Diseases
  作者：Kai Li、Lici A. Schurig-Briccio、Xinxin Feng、Ashutosh Upadhyay、Venugopal Pujari、Benoit Lechartier、Fabio L. Fontes、Hongliang Yang、Guodong Rao、Wei Zhu、Anmol Gulati、Joo Hwan No、Giovana Cintra、Shannon Bogue、Yi-Liang Liu、Katie Molohon、Peter Orlean、Douglas A. Mitchell、Lucio Freitas-Junior、Feifei Ren、Hong Sun、Tong Jiang、Yujie Li、Rey-Ting Guo、Stewart T. Cole、Robert B. Gennis、Dean C. Crick、Eric Oldfield

  DOI：10.1021/jm500131s

  日期：2014.4.10

  We report the discovery of a series of new drug leads that have potent activity against Mycobacterium tuberculosis as well as against other bacteria, fungi, and a malaria parasite. The compounds are analogues of the new tuberculosis (TB) drug SQ109 (1), which has been reported to act by inhibiting a transporter called MmpL3, involved in cell wall biosynthesis. We show that 1 and the new compounds also target enzymes involved in menaquinone biosynthesis and electron transport, inhibiting respiration and ATP biosynthesis, and are uncouplers, collapsing the pH gradient and membrane potential used to power transporters. The result of such multitarget inhibition is potent inhibition of TB cell growth, as well as very low rates of spontaneous drug resistance. Several targets are absent in humans but are present in other bacteria, as well as in malaria parasites, whose growth is also inhibited.