(4E,8E,12E,16E)-20-(methanesulfonyloxy)-4,9,13,17-tetramethylicosa-4,8,1 2,1 6-tetraen-1-yl methanesulfonate

• 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: (4E,8E,12E,16E)-20-(methanesulfonyloxy)-4,9,13,17-tetramethylicosa-4,8,1 2,1 6-tetraen-1-yl methanesulfonate
• 英文别名: (4E,8E,12E,16E)-20-(methanesulfonyloxy)-4,9,13,17-tetramethylicosa-4,8,12,16-tetraen-1-yl methanesulfonate；bis-trisnorsqualenylmethanesulfonate；[(4E,8E,12E,16E)-4,9,13,17-tetramethyl-20-methylsulfonyloxyicosa-4,8,12,16-tetraenyl] methanesulfonate
• 化学式: C₂₆H₄₆O₆S₂
• 分子量: 518.78
• InChiKey: OCWYXDDBWILXOX-OYPPOGAESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  34
• 可旋转键数：
  19
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  104
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (4E,8E,12E,16E)-20-(methanesulfonyloxy)-4,9,13,17-tetramethylicosa-4,8,1 2,1 6-tetraen-1-yl methanesulfonate 在 三甲胺 作用下， 以 乙醇 为溶剂， 反应 120.0h， 以92%的产率得到trimethyl[(4E,8E,12E,16E)-4,9,13,17-tetramethyl-20-(trimethylazaniumyl)icosa-4,8,12,16-tetraen-1-yl]azanium dimethanesulfonate
  参考文献：
  名称：

  [EN] NANOPARTICLES BASED ON A GAG AND A SQUALENE
  [FR] NANOPARTICULES FORMÉES À PARTIR DE GAG ET DE SQUALÈNE

  摘要：

  本发明涉及包含至少一种带负电的糖胺聚糖类大分子或其衍生物的纳米颗粒，非共价结合至少一种由下式（I）所代表的鲨烯性质的阳离子烃基自由基的分子：（I）其中：A、B、C、D、E和F是氢原子或甲基基团；Z和Y代表一个基团（式（II）），一个乙基三烷基铵基团，一个乙基胍基团或1-[乙基亚胺基]胍基团，但至少其中之一与（式（II））不同，符号*表示基团与结构的连接位置；n等于1或2。本发明还涉及制备所述纳米颗粒的方法，以及包含所述纳米颗粒的冻干粉、固体剂量形式和药用或皮肤科组合物。所述纳米颗粒可用作药物，特别是作为抗凝剂。

  公开号：

  WO2014091436A1
• 作为产物：
  描述：

  1,20-bis-trisnorsqualene alcohol 、 甲基磺酰氯 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以67%的产率得到(4E,8E,12E,16E)-20-(methanesulfonyloxy)-4,9,13,17-tetramethylicosa-4,8,1 2,1 6-tetraen-1-yl methanesulfonate
  参考文献：
  名称：

  [EN] NANOPARTICLES BASED ON A GAG AND A SQUALENE
  [FR] NANOPARTICULES FORMÉES À PARTIR DE GAG ET DE SQUALÈNE

  摘要：

  本发明涉及包含至少一种带负电的糖胺聚糖类大分子或其衍生物的纳米颗粒，非共价结合至少一种由下式（I）所代表的鲨烯性质的阳离子烃基自由基的分子：（I）其中：A、B、C、D、E和F是氢原子或甲基基团；Z和Y代表一个基团（式（II）），一个乙基三烷基铵基团，一个乙基胍基团或1-[乙基亚胺基]胍基团，但至少其中之一与（式（II））不同，符号*表示基团与结构的连接位置；n等于1或2。本发明还涉及制备所述纳米颗粒的方法，以及包含所述纳米颗粒的冻干粉、固体剂量形式和药用或皮肤科组合物。所述纳米颗粒可用作药物，特别是作为抗凝剂。

  公开号：

  WO2014091436A1

文献信息

• Nanoparticles based on bioconjugate of GAG
  申请人：Centre National de la Recherche Scientifique

  公开号：EP2742955A1

  公开（公告）日：2014-06-18

  The present invention relates to nanoparticles comprising at least one negatively charged glycosaminoglycan-type macromolecule or a derivative thereof, non-covalently coupled to at least one molecule of a cationic hydrocarbon-based radical of squalene nature represented by the formula (I) which follows: wherein: A, B, C, D, E and F are a hydrogen atom or a methyl group; Z and Y represent a radical an ethyltrialkylammonium radical, an ethylguanidium radical or a 1-[ethylideneamino]guanidinium radical with the proviso that at least one of Z and Y is different from the symbol * showing the position of the attachment of the radical to the structure; and n is equal to 1 or 2. The present invention also relates to a method for preparing said nanoparticles, and to a lyophilisate, a solid dosage form and pharmaceutical or dermatological compositions comprising said nanoparticles. Said nanoparticles are useful as medicines and more particularly as anticoagulant agents.

  本发明涉及含有至少一种带负电荷的糖氨基聚糖类大分子或其衍生物的纳米颗粒，非共价结合至至少一种具有化学式(I)所示的鲨烯性质的阳离子烃基自由基分子，其中： 其中： A、B、C、D、E和F为氢原子或甲基基团；Z和Y代表一个基团，即乙基三烷基铵基团、乙基胍基团或1-[乙基亚氨基]胍基团，但至少其中一个是与*符号不同的附加基团的位置；n等于1或2。 本发明还涉及一种制备上述纳米颗粒的方法，以及含有该纳米颗粒的冻干物、固体剂量形式和药用或皮肤科学组合物。该纳米颗粒可用作药物，特别是作为抗凝剂。
• Novel self assembling nanoparticles for the oral administration of fondaparinux: Synthesis, characterization and in vivo evaluation
  作者：Bettina Ralay-Ranaivo、Didier Desmaële、Elsa P. Bianchini、Elise Lepeltier、Claudie Bourgaux、Delphine Borgel、Thierry Pouget、Jean François Tranchant、Patrick Couvreur、Ruxandra Gref

  DOI：10.1016/j.jconrel.2014.07.060

  日期：2014.11

  Fondaparinux (Fpx) is the anticoagulant of choice in the treatment of short- and medium-term thromboembolic disease. To overcome the low oral bioavailability of Fpx, a new nanoparticulate carrier has been developed. The nanoparticles (NPs) contain squalenyl derivatives, known for their excellent oral bioavailability. They spontaneously self-assemble upon both electrostatic and hydrophobic interactions between the polyanionic Fpx and cationic squalenyl (CSq) derivatives. The preparation conditions were optimized to obtain monodisperse, stable NPs with a mean diameter in the range of 150-200 nm. The encapsulation efficiencies were around 80%. Fpx loadings reached 39 wt.%. According to structural and morphological analysis, Fpx and CSq organized in spherical multilamellar ("onion-type") nanoparticles. Furthermore, in vivo studies in rats suggested that Fpx was well absorbed from the orally administered NPs, which totally dissociated when reaching the blood stream, leading to the release of free Fpx. The Fpx: CSq NPs improved the plasmatic concentration of Fpx in a dose-dependent manner. However, the oral bioavailability of these new NPs remained low (around 0.3%) but of note, the C-max obtained after oral administration of 50 mg/kg NPs was close to the prophylactic plasma concentration needed to treat venous thromboembolism. Moreover, the oral bioavailability of Fpx could be dramatically increased up to 9% by including the nanoparticles into gastroresistant capsules. This study opens up new perspectives for the oral administration of Fpx and paves the way towards elaborating squalene-based NPs which self assemble without the need of covalently grafting the drug to Sq. (C) 2014 The Authors. Published by Elsevier B.V.
• [EN] NANOPARTICLES BASED ON A GAG AND A SQUALENE<br/>[FR] NANOPARTICULES FORMÉES À PARTIR DE GAG ET DE SQUALÈNE
  申请人：CENTRE NAT RECH SCIENT

  公开号：WO2014091436A1

  公开（公告）日：2014-06-19

  The present invention relates to nanoparticles comprising at least one negatively charged glycosaminoglycan-type macromolecule or a derivative thereof, non-covalently coupled to at least one molecule of a cationic hydrocarbon-based radical of squalene nature represented by the formula (I) which follows: (I) wherein: A, B, C, D, E and F are a hydrogen atom or a methyl group; Z and Y represent a radical (formula (II)), an ethyltrialkylammonium radical, an ethylguanidium radical or a 1-[ethylideneamino]guanidinium radical with the proviso that at least one of Z and Y is different from (formula (II)), the symbol * showing the position of the attachment of the radical to the structure; and n is equal to 1 or 2. The present invention also relates to a method for preparing said nanoparticles, and to a lyophilisate, a solid dosage form and pharmaceutical or dermatological compositions comprising said nanoparticles. Said nanoparticles are useful as medicines and more particularly as anticoagulant agents.

  本发明涉及包含至少一种带负电的糖胺聚糖类大分子或其衍生物的纳米颗粒，非共价结合至少一种由下式（I）所代表的鲨烯性质的阳离子烃基自由基的分子：（I）其中：A、B、C、D、E和F是氢原子或甲基基团；Z和Y代表一个基团（式（II）），一个乙基三烷基铵基团，一个乙基胍基团或1-[乙基亚胺基]胍基团，但至少其中之一与（式（II））不同，符号*表示基团与结构的连接位置；n等于1或2。本发明还涉及制备所述纳米颗粒的方法，以及包含所述纳米颗粒的冻干粉、固体剂量形式和药用或皮肤科组合物。所述纳米颗粒可用作药物，特别是作为抗凝剂。