artesunic acid | 182824-33-5

• 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: artesunic acid
• 英文别名: artesunate；ARS；ART；artensunate；4-oxo-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]oxy]butanoic acid
• CAS: 182824-33-5
• 化学式: C₁₉H₂₈O₈
• 分子量: 384.427
• InChiKey: FIHJKUPKCHIPAT-AXFKQHSWSA-N

物化性质

• 熔点：
  97.6-98.2 °C(Solv: ethyl acetate (141-78-6); hexane (110-54-3))
• 沸点：
  507.1±50.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  8

ADMET

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用概述：有限的信息表明，母亲口服200毫克的剂量在乳汁中产生较低水平，预计不会对哺乳婴儿造成任何不良影响，尤其是如果婴儿年龄超过2个月。在服用剂量后6小时内不进行哺乳，可以显著减少婴儿接受的剂量。 总的来说，哺乳期妇女的乳汁中会分泌非常少量的抗疟疾药物。由于通过母乳转移的抗疟疾药物量不足以提供对疟疾的充分保护，需要化学预防的婴儿必须接受推荐剂量的抗疟疾药物。 ◉ 对哺乳婴儿的影响：接受二氢青蒿素和哌喹作为疟疾治疗的哺乳婴儿，比不服药的非哺乳婴儿出现呕吐的频率更高。这一发现是否适用于通过母乳接受二氢青蒿素的婴儿尚未进行研究。 ◉ 对泌乳和母乳的影响：截至修订日期，未找到相关的已发布信息。

◉ Summary of Use during Lactation:Limited information indicates that a maternal dose of 200 mg orally produced low levels in milk and would not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months. Withholding breastfeeding for 6 hours after a dose should markedly reduce the dose the infant receives. In general, very small amounts of antimalarial drugs are excreted in the breast milk of lactating women. Because the quantity of antimalarial drugs transferred in breast milk is insufficient to provide adequate protection against malaria, infants who require chemoprophylaxis must receive the recommended dosages of antimalarial drugs. ◉ Effects in Breastfed Infants:Breastfed infants who were given dihydroartemisinin and piperaquine as a treatment for malaria had a higher frequency of vomiting than non-breastfed infants given the drugs. Whether this finding applies to infants who receive dihydroartemisinin via breastmilk has not been studied. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

反应信息

• 作为反应物：
  描述：

  artesunic acid 在 4-二甲氨基吡啶 、 氧气 、 uranyl(VI) acetate dihydrate 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 邻二甲苯 、 水 、 乙腈 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 生成 3-(methylsulfonyl)propyl ((3R,5aS,6R,8aS,9R,10S,12aR)-3,6,9-trimethyldecahydro-12H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl) succinate
  参考文献：
  名称：

  铀酰光催化作用的基态氧对硫化物的选择性后期加氧。

  摘要：

  氧合是合成中的基本转变。在这里，我们描述了在环境条件下用基态氧对含硫配合物分子的选择性后期氧合。活性铀酰阳离子（UO2 2+）的高氧化势使砜的有效合成成为可能。假设O = U = O组中从O 2p到U 5f的配体到金属的电荷转移过程（LMCT）会产生UV中心和一个氧自由基，并且受溶剂和添加剂的影响，并且可以调整以促进选择性硫氧化。这种可调策略可以通过后期氧合以原子和步长高效的方式分批合成32种药物和类似物。

  DOI：

  10.1002/anie.201906080
• 作为产物：
  描述：

  丁二酸 、 dihydroartesiminin 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三氯乙腈 作用下， 以 二氯甲烷 为溶剂， 以17 %的产率得到artesunic acid
  参考文献：
  名称：

  CN116284039

  摘要：

  公开号：

文献信息

• 一种喜树碱与青蒿琥酯偶联物及其制备方法与 应用
  申请人：浙江工业大学

  公开号：CN104163823B

  公开（公告）日：2016-03-09

  本发明公开了一种式(I)所示的喜树碱与青蒿琥酯偶联物，其制备方法为：将式(II)所示喜树碱和式(III)所示青蒿琥酯溶于有机溶剂中，在1-乙基-(3-二甲基氨基丙基)碳二亚胺盐酸盐和4-二甲氨基吡啶的作用下，于15～50℃搅拌反应，TLC跟踪监测至反应不再进行，反应液后处理，即得式(I)所示的喜树碱与青蒿琥酯偶联物；本发明喜树碱与青蒿琥酯偶联物可用于制备抗肿瘤药物；
• [EN] NANOPARTICLES FOR CHEMOTHERAPY, TARGETED THERAPY, PHOTODYNAMIC THERAPY, IMMUNOTHERAPY, AND ANY COMBINATION THEREOF<br/>[FR] NANOPARTICULES POUR CHIMIOTHÉRAPIE, THÉRAPIE CIBLÉE, THÉRAPIE PHOTODYNAMIQUE, IMMUNOTHÉRAPIE ET N'IMPORTE QUELLE COMBINAISON DE CES DERNIÈRES
  申请人：UNIV CHICAGO

  公开号：WO2017201528A1

  公开（公告）日：2017-11-23

  Prodrugs containing lipid moieties attached to drug derivatives, such as anti-cancer drug derivatives, via linkers comprising disulfide groups are described. Also described are nanoparticles coated with a lipid layer containing the prodrugs, formulations comprising the nanoparticles, and the use of the nanoparticles in methods of treating diseases, such as cancer, alone or in combination with additional drug compounds, targeting agents, and/or immunotherapy agents, such as immunosuppression inhibitors that target the CTLA-4, PD-1/PD-L1, IDO, LAG-3, CCR-7 or other pathways, or multiple immunosuppression inhibitors targeting a combination of such pathways. Optionally, the nanoparticles can comprise a photosensitizer or a derivative thereof and can be used in methods involving photodynamic therapy. Synergistic therapeutic effects result from combinations of multiple modalities provided by the disclosed nanoparticles and/or nanoparticle formulations.

  含有脂质基团连接到药物衍生物的前药，例如通过含有二硫键的连接剂连接到抗癌药物衍生物的前药被描述。还描述了涂有含有前药的脂质层的纳米粒子，包含这些纳米粒子的配方，以及在治疗疾病的方法中使用这些纳米粒子，例如癌症，单独或与额外的药物化合物、靶向剂和/或免疫疗法剂联合使用，例如靶向CTLA-4、PD-1/PD-L1、IDO、LAG-3、CCR-7或其他途径的免疫抑制抑制剂，或者靶向这些途径的多种免疫抑制抑制剂的组合。可选地，纳米粒子可以包含光敏剂或其衍生物，并可用于涉及光动力疗法的方法。由所披露的纳米粒子和/或纳米粒子配方提供的多种疗法模式的组合导致协同治疗效果。
• Antibacterial Barbituric Acid Analogues Inspired from Natural 3-Acyltetramic Acids; Synthesis, Tautomerism and Structure and Physicochemical Property-Antibacterial Activity Relationships
  作者：Yong-Chul Jeong、Mark Moloney

  DOI：10.3390/molecules20033582

  日期：——

  The synthesis, tautomerism and antibacterial activity of novel barbiturates is reported. In particular, 3-acyl and 3-carboxamidobarbiturates exhibited antibacterial activity, against susceptible and some resistant Gram-positive strains of particular interest is that these systems possess amenable molecular weight, rotatable bonds and number of proton-donors/acceptors for drug design as well as less

  报道了新型巴比妥酸盐的合成、互变异构和抗菌活性。特别是，3-酰基和 3-羧酰胺巴比妥酸盐对敏感和一些耐药革兰氏阳性菌株表现出抗菌活性，特别令人感兴趣的是，这些系统具有适用的分子量、可旋转键和用于药物设计的质子供体/受体数量由于亲脂性较差，理化性质和离子状态类似于目前用于口服和注射的抗生素。不幸的是，巴比妥核心对血浆蛋白亲和力的降低不足以实现体内活性。因此需要进一步优化以降低血浆蛋白亲和力和/或提高抗生素效力，
• Novel spiro-1,2,4-trioxanes
  申请人：Singh Chandan

  公开号：US20070191475A1

  公开（公告）日：2007-08-16

  The present invention relates to spiro 1,2,4-trioxanes of general formula 4. This invention more particularly relates to a process for the preparation of a series of spiro 1,2,4-trioxanes. Wherein, Ar represents aryl groups such as phenyl, 4-biphenyl, 4-chlorophenyl, 4-methoxyphenyl, 4-methylphenyl, 4-cyclohexylphenyl, 1-naphthyl, 2-naphthyl and the like and R represents hydrogen or the alkyl group such as methyl, ethyl and the like. Several of these compounds show high order of antimalarial activity against multidrug-resistant malaria in mice and thus hold promise as antimalarial agents against multidrug-resistant malaria.

  本发明涉及一般式4的螺环1,2,4-三氧杂环丙烷。该发明更具体地涉及一种制备一系列螺环1,2,4-三氧杂环丙烷的方法。其中，Ar代表芳基团，如苯基、4-联苯基、4-氯苯基、4-甲氧基苯基、4-甲基苯基、4-环己基苯基、1-萘基、2-萘基等，R代表氢或烷基，如甲基、乙基等。这些化合物中的几种显示出高度的抗疟活性，对多药耐药性疟疾在小鼠中具有作用，并因此有望作为抗多药耐药性疟疾的抗疟药物。
• DUAL MOLECULES CONTAINING A PEROXIDE DERIVATIVE, THEIR SYNTHESIS AND THERAPEUTIC USES
  申请人：COSLEDAN Frederic

  公开号：US20120122923A1

  公开（公告）日：2012-05-17

  The invention concerns dual molecules corresponding to formula (I): in which: A represents a molecular residue with antimalarial activity of formula (IIa) or (IIIa) or a residue facilitating bioavailability; B represents a cycloalkyl group potentially substituted, or B represents a bi- or tricyclic group capable of being substituted, or B represents 2 cycloalkyl groups linked together through either a single bond or an alkylene chain; m and n represent independently of one another 0, 1 or 2; R 5 represents a hydrogen atom, an alkyl, cycloalkyl or C 1-3 -alkylene-cycloakyl group; Z 1 and Z 2 represent an alkyl radical, the group Z 1 +Z 2 +C i +C j representing a mono- or polycyclic structure, with one of the Z 1 or Z 2 being able to represent a single bond; R 1 and R 2 , identical or different, represent a hydrogen atom or a functional group capable of increasing hydrosolubility; R x and R y forming together a cyclic peroxide including 4 to 8 links and including 1 or 2 additional oxygen atoms in the cyclic structure, possibly substituted by one or more R 3 groups; as a base or a salt to be added to an acid, as a hydrate or solvate, in racemic form, isomers and their mixtures, in addition to their diasteroisomers and their mixtures. Preparation method and use as medications with antimalarial activity.

  本发明涉及与式(I)相对应的双分子，其中：A代表具有抗疟活性的分子残基，其化学式为(IIa)或(IIIa)，或者代表有助于生物利用度的残基；B代表可能被取代的环烷基团，或者B代表可能被取代的双环或三环基团，或者B代表通过单键或烷基链连接在一起的2个环烷基团；m和n分别独立地表示0、1或2；R5代表氢原子、烷基、环烷基或C1-3-烷基-环烷基团；Z1和Z2代表烷基基团，Z1+Z2+Ci+Cj代表单环或多环结构，其中Z1或Z2之一可以表示单键；R1和R2，相同或不同，代表氢原子或能增加水溶性的功能基团；Rx和Ry共同形成一个包含4到8个链的环过氧化物，包括环结构中的1或2个额外氧原子，可能被一个或多个R3基团取代；作为酸的碱或盐形式，作为水合物或溶剂合物，以外消旋形式、同分异构体及其混合物，以及它们的对映异构体及其混合物。制备方法和用作具有抗疟活性的药物。