2-((3R, 5aS, 6R, 8aS, 9R,10R, 12R, 12aR)-3,6,9-trimethyldecahydro-12H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl)acetic acid | 161562-97-6

• 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: 2-((3R, 5aS, 6R, 8aS, 9R,10R, 12R, 12aR)-3,6,9-trimethyldecahydro-12H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl)acetic acid
• 英文别名: 2-[(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]acetic acid
• CAS: 161562-97-6
• 化学式: C₁₇H₂₆O₆
• 分子量: 326.39
• InChiKey: YGOJHRLFJFDYCJ-LBYUOYBLSA-N

物化性质

• 沸点：
  447.4±45.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  23
• 可旋转键数：
  2
• 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：

  2-((3R, 5aS, 6R, 8aS, 9R,10R, 12R, 12aR)-3,6,9-trimethyldecahydro-12H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl)acetic acid 在 lithium aluminium tetrahydride 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 8.0h， 生成 10-(2-oxoethyl)deoxoartemisinin
  参考文献：
  名称：

  Novel Endoperoxide-Based Transmission-Blocking Antimalarials with Liver- and Blood-Schizontocidal Activities

  摘要：

  In a search for effective compounds against both the blood- and liver-stages of infection by malaria parasites with the ability to block the transmission of the disease to mosquito vectors, a series of hybrid compounds combining either a 1,2,4-trioxane or 1,2,4,5-tetraoxane and 8-aminoquinoline moieties were synthesized and screened for their antimalarial activity. These hybrid compounds showed high potency against both exoerythrocytic and erythrocytic forms of malaria parasites, comparable to representative trioxane-based counterparts. Furthermore, they efficiently blocked the development of the sporogonic cycle in the mosquito vector. The tetraoxane-based hybrid 5, containing an amide linker between the two moieties, effectively cleared a patent blood-stage P. berghei infection in mice after i.p. administration. Overall, these results indicate that peroxide-8-aminoquinoline hybrids are excellent starting points to develop an agent that conveys all the desired antimalarial multistage activities in a single chemical entity and, as such, with the potential to be used in malaria elimination campaigns.

  DOI：

  10.1021/ml4002985
• 作为产物：
  描述：

  双氢青蒿素 在 吡啶 、 potassium permanganate 、 sodium periodate 、 zinc(II) chloride 作用下， 以 二氯甲烷 、 水 、 1,2-二氯乙烷 、 丙酮 为溶剂， 反应 48.0h， 生成 2-((3R, 5aS, 6R, 8aS, 9R,10R, 12R, 12aR)-3,6,9-trimethyldecahydro-12H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl)acetic acid
  参考文献：
  名称：

  Facile synthesis and anticancer activity of C-10 non-acetal deoxoartemisinin dimers

  摘要：

  In this research, N-(2-aminoethyl)glycine-linked C-10 non-acetal deoxoartemisinin dimers were synthesized by using solution phase peptide synthesis approach. In addition, chemical modification of the C-10 non-acetal deoxoartemisinin monomers and dimers by adding a lysine unit to the N-terminus has been performed. The biological activities of all synthesized compounds were evaluated against the colon cancer cell line (Caco-2). The non-acetal deoxoartemisinin monomers 12a, 15a-c and dimers 13a, 16a-c were active against Caco-2 cells and more potent than dihydroartemisinin. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.020

文献信息

• Artemisinin-Polypyrrole Conjugates: Synthesis, DNA Binding Studies and Preliminary Antiproliferative Evaluation
  作者：Louise La Pensée、Sunil Sabbani、Raman Sharma、Inder Bhamra、Emma Shore、Amy E. Chadwick、Neil G. Berry、James Firman、Nuna C. Araujo、Lília Cabral、Maria L. S. Cristiano、Cerys Bateman、Omar Janneh、Adelina Gavrila、Yi Hang Wu、Afthab Hussain、Stephen A. Ward、Paul A. Stocks、Rick Cosstick、Paul M. O'Neill

  DOI：10.1002/cmdc.201200536

  日期：2013.5

  trials against breast, colorectal and non‐small‐cell lung cancers. In an attempt to offer increased specificity, a series of hybrid artemisinin–polypyrrole minor groove binder conjugates are described. DNA binding/modelling studies and preliminary biological evaluation give insights into their mechanism of action and the potential of this strategy.

  大于其各部分的总和：青蒿素目前正处于针对乳腺癌、结直肠癌和非小细胞肺癌的 I-II 期临床试验中。为了提供更高的特异性，描述了一系列混合青蒿素-聚吡咯小沟结合剂偶联物。DNA 结合/建模研究和初步生物学评估可以深入了解其作用机制和该策略的潜力。
• Synthesis of Tamoxifen‐Artemisinin and Estrogen‐Artemisinin Hybrids Highly Potent Against Breast and Prostate Cancer
  作者：Tony Fröhlich、Christina Mai、Roman P. Bogautdinov、Svetlana N. Morozkina、Alexander G. Shavva、Oliver Friedrich、Daniel F. Gilbert、Svetlana B. Tsogoeva

  DOI：10.1002/cmdc.202000174

  日期：2020.8.5

  for new and effective treatments of breast and prostate cancer, a series of hybrid compounds based on tamoxifen, estrogens, and artemisinin were successfully synthesized and analyzed for their in vitro activities against human prostate (PC‐3) and breast cancer (MCF‐7) cell lines. Most of the hybrid compounds exhibit a strong anticancer activity against both cancer cell lines – for example, EC50 (PC‐3)

  在寻找新的、有效的乳腺癌和前列腺癌治疗方法的过程中，成功合成了一系列基于他莫昔芬、雌激素和青蒿素的混合化合物，并分析了它们对人前列腺癌 (PC-3) 和乳腺癌 (MCF) 的体外活性。 ‐7) 细胞系。大多数杂化化合物对两种癌细胞系都表现出很强的抗癌活性——例如，EC 50 (PC-3) 低至 1.07 μM，EC 50 (MCF-7) 低至 2.08 μM——因此表现出比它们更高的活性。母体化合物 4-羟基他莫昔芬（阿莫昔芬，7；EC 50 =75.1 (PC-3) 和 19.3 μM (MCF-7)），二氢青蒿素 ( 2；EC 50 =263.6 (PC-3) 和 49.3 μM (MCF-7) ）和青蒿酸（3；EC 50 =195.1（PC-3）和32.0 μM（MCF-7））。最有效的化合物是抗前列腺癌的雌激素-青蒿素杂合体27和28（EC 50 = 1.18 和 1.07 μM），以及抗乳腺癌的杂合体23（EC
• Synthesis of Thymoquinone–Artemisinin Hybrids: New Potent Antileukemia, Antiviral, and Antimalarial Agents
  作者：Tony Fröhlich、Christoph Reiter、Mohamed E. M. Saeed、Corina Hutterer、Friedrich Hahn、Maria Leidenberger、Oliver Friedrich、Barbara Kappes、Manfred Marschall、Thomas Efferth、Svetlana B. Tsogoeva

  DOI：10.1021/acsmedchemlett.7b00412

  日期：2018.6.14

  HCMV. In addition, hybrids 6a/b possessed excellent antimalarial activity (EC50 = 5.9/3.7 nM), which was better than that of artesunic acid (EC50 = 8.2 nM) and chloroquine (EC50 = 9.8 nM). Overall, most of the presented thymoquinone-artemisinin-based hybrids exhibit an excellent and broad variety of biological activities (anticancer, antimalarial, and antiviral) combined with a low toxicity/high selectivity

  合成了一系列基于天然产物青蒿素和胸腺醌的杂合化合物，并研究了它们对疟原虫恶性疟原虫3D7株，人巨细胞病毒（HCMV）和两种白血病细胞系（药物敏感性CCRF-CEM和多药）的生物学活性耐性子线CEM / ADR5000）。开发了一种前所未有的一锅法，从C-10α-与C-10β-二氢青蒿素的1：1混合物开始选择性形成C-10α-乙酸酯14。这种简便方法的关键步骤是由DCC / DMAP介导的丙二酸的轻度脱羧活化。醚连接的胸腺醌-青蒿素杂种6a / b在所有类别中均是最活跃的化合物，但对健康的人包皮成纤维细胞没有毒副作用，因此具有选择性。他们展示的EC50值为0。2μM对阿霉素敏感性以及对多药耐药的白血病细胞有抗药性，因此可以认为优于阿霉素。而且，它们显示出的抗HCMV活性比标准药物更昔洛韦高五倍，活性比青蒿酸高近八倍。此外，杂种6a / b具有出色的抗疟活性（EC50 = 5.9 / 3.7 nM），优于青蒿琥酯酸（EC50
• 新型青蒿素衍生物及其制法和应用
  申请人：中国科学院上海生命科学研究院

  公开号：CN103570738B

  公开（公告）日：2016-04-13

  本发明涉及新型青蒿素衍生物及其制法和应用。具体地，本发明公开了一类结构如式I所示的青蒿素衍生物或其药学上可接受的盐，或其对映异构体、非对映异构体或外消旋体，其中X、Y、Z、n、k、P如本文中定义。本发明还公开了所述化合物的制法及其应用，所述化合物对治疗肿瘤有优异的效果。
• Identification of HSP90 as a direct target of artemisinin for its anti-inflammatory activity <i>via</i> quantitative chemical proteomics
  作者：Guolin Wu、Bao Cheng、Hui Qian、Shengming Ma、Qin Chen

  DOI：10.1039/c9ob01264h

  日期：——

  Global profiling of the target proteins of ART for its anti-inflammatory activity via ABPP combined with quantitative chemical proteomics.

  通过ABPP结合定量化学蛋白质组学对ART的靶蛋白进行全球研究，以探究其抗炎活性。