3-(10-deoxoartemisin-10-yl)propanoic acid | 508234-34-2

• 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: 3-(10-deoxoartemisin-10-yl)propanoic acid
• 英文别名: ART-EtC(O)-OH；3-[(1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl]propanoic acid
• CAS: 508234-34-2
• 化学式: C₁₈H₂₈O₆
• 分子量: 340.417
• InChiKey: QXSPUCZBSKCHDP-ZINAWWQHSA-N

物化性质

• 沸点：
  448.2±45.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  74.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(10-deoxoartemisin-10-yl)propanoic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 生成 3-n-propyl sulfone
  参考文献：
  名称：

  一种 6 mg/kg 的新型单体硫化物三恶烷与甲氟喹的口服剂量可完全治愈感染疟疾的小鼠

  摘要：

  制备了 16 种新的天然三恶烷青蒿素的苯胺衍生物，并评估了对伯氏疟原虫感染小鼠的抗疟功效。在这 16 种新的苯胺以 6 mg/kg 剂量与盐酸甲氟喹联合 18 mg/kg 口服给药的情况下，只有硫化物 3-arteSanilide 12d完全治愈：在感染后第 30 天，该组中的所有小鼠均未检测到寄生虫血症，获得与未感染的对照小鼠一样重，并且表现正常。

  DOI：

  10.1021/jm201214d
• 作为产物：
  描述：

  dihydroartemisinin 在 吡啶 、 ruthenium trichloride 、 sodium periodate 、 dimethyl sulfide borane 、 zinc(II) chloride 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙酸乙酯 、 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 22.0h， 生成 3-(10-deoxoartemisin-10-yl)propanoic acid
  参考文献：
  名称：

  Synthesis of Novel G Factor or Chloroquine-Artemisinin Hybrids and Conjugates with Potent Antiplasmodial Activity

  摘要：

  A series of novel hybrids of artemisinin (ART) with either a phytormone endoperoxide G factor analogue (GMeP) or chloroquine (CQ) and conjugates of the same compounds with the polyamines (PAs), spermidine (Spd), and homospermidine (Hsd) were synthesized and their antiplasmodial activity was evaluated using the CQ-resistant P. falciparum FcB1/Colombia strain. The ART-GMeP hybrid 5 and compounds 9 and 10 which are conjugates of Spd and Hsd with two molecules of ART and one molecule of GMeP, were the most potent with IC50 values of 2.6, 8.4, and 10.6 nM, respectively. The same compounds also presented the highest selectivity indexes against the primary human fibroblast cell line AB943 ranging from 16 372 for the hybrid 5 to 983 for the conjugate 10 of Hsd.

  DOI：

  10.1021/acsmedchemlett.9b00669

文献信息

• Malaria-Infected Mice Live until at Least Day 30 after a New Monomeric Trioxane Combined with Mefloquine Are Administered Together in a Single Low Oral Dose
  作者：Lauren E. Woodard、Wonsuk Chang、Xiaochun Chen、Jun O. Liu、Theresa A. Shapiro、Gary H. Posner

  DOI：10.1021/jm9005934

  日期：2009.12.10

  from the natural trioxane artemisinin, the thermally and hydrolytically stable trioxane fluoroanilide 4b has been prepared. Upon one oral dose of only 6.8 mg/kg of monomeric trioxane 4b combined with 20 mg/kg of mefloquine hydrochloride, all of the malaria-infected mice lived until at least day 30 post infection. Of the five mice in this surviving group, four (80%) were completely cured (no parasites

  仅通过五个简单的步骤，天然三恶烷青蒿素的总产率为 48%，即可制备出热稳定和水解稳定的三恶烷氟苯胺4b。在一次口服剂量仅为 6.8 mg/kg 的单体三恶烷4b与 20 mg/kg 的盐酸甲氟喹组合后，所有感染疟疾的小鼠都至少活到感染后第 30 天。在这个存活组的五只小鼠中，四只（80%）完全治愈（血液中没有寄生虫），一只老鼠有 4% 的血液寄生虫血症。重要的是，这种使用单体三恶烷4b加盐酸甲氟喹的ACT 化疗的疗效明显优于相同条件下使用流行的三恶烷药物蒿甲醚加盐酸甲氟喹的疗效。
• Discovery of Artemisinin-Glycolipid Hybrids as Anti-oral Cancer Agents
  作者：Jérémy Ricci、Minkyu Kim、Won-Yoon Chung、Kwang-Kyun Park、Mankil Jung

  DOI：10.1248/cpb.59.1471

  日期：——

  Novel artemisinin-glycolipid hybrids were directly synthesized from 12β (C–C)-type deoxoartemisinin and glycolipid and exhibited exceptional in vitro anticancer activity, particularly against the oral carcinoma cancer cell lines, respectively. The artemisinin-glycolipid hybrids, with effective concentrations under 20 μM, demonstrated better anticancer activity than either artemisinin or glycolipid alone and showed five times more anti-oral cancer activity than either cisplatin or paclitaxel.

  由12β (C-C)型脱氧青蒿素和糖脂直接合成的新型青蒿素-糖脂混合物，在体外表现出卓越的抗癌活性，尤其是对口腔癌癌细胞株的抗癌活性。青蒿素-糖脂混合物的有效浓度低于 20 μ<小>M，比单独使用青蒿素或糖脂具有更好的抗癌活性，其抗口腔癌活性是顺铂或紫杉醇的五倍。
• Antitumor Activity of Novel Deoxoartemisinin Monomers, Dimers, and Trimer
  作者：Mankil Jung、Sangmin Lee、Jungyeob Ham、Kyunghoon Lee、Hanjo Kim、Soo Kie Kim

  DOI：10.1021/jm020119d

  日期：2003.3.1

  The first primary amines 9 and bromoalkyl analogues 7 of deoxoartemisinin with nonacetal functionality at C-12 are prepared as versatile intermediates for the synthesis of various derivatives. Eight C-12 nonacetal type dimers and one trimer of deoxoartemisinin were prepared using novel chemistry. Dimers, particularly 12a, 18a,b, and trimer 17, were especially potent and selective at inhibiting the growth of certain human cancer cell lines and were comparable to that of clinically used anticancer drugs. The linker with one amide- or one sulfur-centered two ethylene groups of the dimers is essential for high anticancer activity. Trimer 17 shows very potent activity against most of the human cancer cell lines tested.
• [EN] TRIOXANE MONOMERS AND DIMERS<br/>[FR] MONOMÈRES ET DIMÈRES À BASE DE TRIOXANE
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2010135427A3

  公开（公告）日：2011-04-21
• [EN] MONOMERIC TRIOXANE AMIDE SULFUR COMPOUNDS<br/>[FR] COMPOSÉS DE SOUFRE D'AMIDE DE TRIOXANE MONOMÈRE
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2012142575A3

  公开（公告）日：2013-04-04