Artelinic acid

• 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: Artelinic acid
• 英文别名: 4-[[(3R,5aS,6R,8aS,9R,10S,12R,12aR)-decahydro-3,6,9-trimethyl-3,12-epoxy-12H-pyrano[4,3-f]-1,2-benzodioxepin-10-yl]oxy]methylbenzoic acid；Artelinic_acid；4-[[(1S,4S,5R,8S,9R,10S,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl]oxymethyl]benzoic acid
• 化学式: C₂₃H₃₀O₇
• 分子量: 418.487
• InChiKey: UVNHKOOJXSALHN-DPLKYLHHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  83.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Artelinic acid 在 human liver microsomes 作用下， 反应 0.5h， 生成 dihydroartemisinin
  参考文献：
  名称：

  Metabolism of artelinic acid to dihydroqinghaosu by human liver cytochrome P4503A

  摘要：

  1. Artelinic acid (AL), a water-soluble artemisinin analogue for treatment of multidrug resistant malaria, is metabolized to the active metabolite dihydroqinghaosu (DQHS) solely by CYP3A4/5. Although AL is not metabolized by CYP2C9, it does inhibit diclofenac 4-hydroxylase activity with an IC50= 115 mu M. Interestingly, AL activates CYP2D6-mediated bufuralol metabolism in human liver microsomes but not recombinant CYP2D6-Val by similar to 30% at AL concentrations up to 100 mu M.2. In human liver microsomes, AL is metabolized to DQHS with a K-m, = 157 +/- 44 mu M I and V-max = 0.77+/-0.56 nmol DQHS/min/mg protein. Human recombinant CYP3A4 catalysed the conversion of AL to DQHS with a K-m,= 102+/-23 mu M and a I 1.96+/-0.38 nmol DQHS/min/nmol P450. The kinetic parameters (K-m and V-max) for DQHS formation from CYP3A5 were 189+/-19 mu M and 3.60+/-0.42 nmol DQHS/min/nmol P450 respectively.3. Inhibition studies suggest that azole antifungals and calcium channel blockers may present clinically significant drug-drug interactions. In human liver microsomes, ketoconazole and miconazole were potent competitive inhibitors of DQHS formation with a K-1 = 0.028 and 0.124 mu M respectively. Verapamil is a non-competitive inhibitor of DQHS formation in human liver microsomes with a K-m = 15 mu M.

  DOI：

  10.1080/004982599238335
• 作为产物：
  描述：

  artemisinin 在 盐酸 、 sodium tetrahydroborate 、 lithium chloride 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 生成 Artelinic acid
  参考文献：
  名称：

  Method and apparatus for the synthesis of dihydroartemisinin and artemisinin derivatives

  摘要：

  本发明涉及一种连续生产二氢青蒿素以及由二氢青蒿素衍生的青蒿素衍生物的方法，该方法利用青蒿素或二氢青蒿酸（DHAA）作为起始物质，并且涉及一种用于生产二氢青蒿素以及青蒿素衍生物的连续流反应器。发现在连续过程中将青蒿素还原为二氢青蒿素需要一种特殊类型的反应器以及包括氢化还原剂、至少一种活化剂（如无机活化剂）、至少一种固体碱、至少一种无水溶剂和至少一种C1-C5醇的特殊组合的试剂。

  公开号：

  EP2826779A1

文献信息

• EP2717879B1
  申请人：——

  公开号：EP2717879B1

  公开（公告）日：2017-08-16
• Artemisinin And Its Derivatives For Use In The Treatment Of Kidney Disease
  申请人：QUEEN MARY & WESTFIELD COLLEGE, UNIVERSITY OF LONDON

  公开号：US20150335612A1

  公开（公告）日：2015-11-26

  The present invention relates compounds according to Formula (I) wherein R 1 and R 2 are independently H or an optionally substituted group selected from an alkyl, a heteroalkyl, an aryl, a heteroaryl, an arylalkyl, and a heteroarylalkyl, and R 3 and R 4 taken together form a carbonyl (═O); or wherein R 1 and R 2 are independently H or an optionally substituted group selected from an alkyl, a heteroalkyl, an aryl, a heteroaryl, an arylalkyl, and a heteroarylalkyl, R 3 is H and R 4 is H or —OR 5 , wherein R 5 is H or an optionally substituted group selected from an alkyl, a heteroalkyl, an aryl, a heteroaryl, an arylalkyl, and a heteroarylalkyl; or pharmaceutically acceptable salts or esters thereof, for use in the treatment of kidney disease, in particular in the treatment of acute kidney injury. The present invention also relates to methods of treatment of the same and methods of kidney transplant surgery and coronary artery bypass graft surgery using the compounds of Formula (I).
• Artemisinin And Its Derivatives For Use In The Treatment Of Trauma Haemorrhage And Associated Conditions
  申请人：Queen Mary University of London

  公开号：US20170182000A1

  公开（公告）日：2017-06-29

  The present invention relates to the treatment of trauma haemorrhage or trauma haemorrhage-induced organ injury and associated disorders (in particular stoke, burns and brain injury) using the anti-malarial compound artemisinin and its derivatives. The present invention also relates to the treatment of myocardial infarction and coronary heart disease (and associated disorders) using the anti-malarial compound artemisinin and its derivatives. The present invention also relates to the use of artemisinin and its derivatives in coronary artery bypass surgery, heart transplantation, and diseases associated with ischaemia-reperfusion.
• US9603831B2
  申请人：——

  公开号：US9603831B2

  公开（公告）日：2017-03-28
• US9949948B2
  申请人：——

  公开号：US9949948B2

  公开（公告）日：2018-04-24