(4E,8E,12E,16E)-4,8,13,17,21-pentamethyldocosa-4,8,12,16,20-pentaen-1-yl methanesulfonate | 151671-34-0

• 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)-4,8,13,17,21-pentamethyldocosa-4,8,12,16,20-pentaen-1-yl methanesulfonate
• 英文别名: (4E,8E,12E,16E)-4,8,13,17,21-pentamethyl-4,8,12,16,20-docosapentaenyl methanesulfonate；1,1′,2-trisnorsqualenyl methanesulfonate；trisnorsqualenyl methanesulfonate；1,1',2-trisnorsqualenyl methanesulfonate；1,1′,2-trisnorsqualenyl mesylate；[(4E,8E,12E,16E)-4,8,13,17,21-pentamethyldocosa-4,8,12,16,20-pentaenyl] methanesulfonate
• CAS: 151671-34-0
• 化学式: C₂₈H₄₈O₃S
• 分子量: 464.753
• InChiKey: UZNRDCWRIXNCBL-BANQPHDMSA-N

物化性质

• 沸点：
  569.9±39.0 °C(Predicted)
• 密度：
  0.957±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  9.4
• 重原子数：
  32
• 可旋转键数：
  17
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  51.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4E,8E,12E,16E)-4,8,13,17,21-pentamethyldocosa-4,8,12,16,20-pentaen-1-yl methanesulfonate 在 potassium tert-butylate 作用下， 以 乙腈 、 xylene 为溶剂， 反应 24.5h， 生成 {2,3-bis[(4E,8E,12E,16E)-4,8,13,17,21-pentamethyl-4,8,12,16,20-docosapentaenyloxy]propyl}(2-hydroxyethyl)dimethylammonium bromide
  参考文献：
  名称：

  Synthesis, characterization and transfection activity of new saturated and unsaturated cationic lipids

  摘要：

  We synthesized new cationic lipids, analogue to N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA) and 1,2-dimyristyloxypropyl-3-dimethyl-hydroxyethylammonium bromide (DMRIE), in order to compare those containing a dodecyl chain with those having a relatively long chain with two or five double bonds, such as squalenyl and dihydrofarnesyl derivatives, or complex saturated structures, such as squalane derivatives. The fusogenic helper lipid dioleoylphosphatidylethanolamine (DOPE) was added to cationic lipids to form a stable complex. Liposomes composed of 50:50 w/w cationic lipid/DOPE were prepared and incubated with plasmidic DNA at various charge ratios and the diameter and zeta potential of the complexes were measured. The surface charge of the DNA/lipid complexes can be controlled by adjusting the cationic lipid/DNA ratio. Finally, we tested the in vitro transfection efficiency of the cationic lipid/DNA complexes using different cell lines. The transfection efficiency was highest for the dodecyloxy derivative containing a single hydroxyethyl group in the head, followed by the dodecyloxy and the farnesyloxy trimethylammonium derivatives. Instead the C27 squalenyl and C27 squalanyl derivatives resulted inactive.

  DOI：

  10.1016/j.farmac.2004.06.007
• 作为产物：
  描述：

  2,3环氧角鲨烯 在 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 过碘酸 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 (4E,8E,12E,16E)-4,8,13,17,21-pentamethyldocosa-4,8,12,16,20-pentaen-1-yl methanesulfonate
  参考文献：
  名称：

  Nanoparticles based on bioconjugate of GAG

  摘要：

  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。

  公开号：

  EP2742955A1

文献信息

• Multifunctional squalene-based prodrug nanoparticles for targeted cancer therapy
  作者：Duc Trung Bui、Julien Nicolas、Andrei Maksimenko、Didier Desmaële、Patrick Couvreur

  DOI：10.1039/c3cc47427e

  日期：——

  Fluorescent and biotinylated squalene–gemcitabine prodrug nanoparticles exhibiting high drug payloads have been prepared and successfully used to target different cancer cell lines, resulting in increased cell uptake and improved anticancer efficiency, which represents the first targeted system derived from the squalenoylation approach.

  制备了具有高药物负载的荧光标记及生物素化角鲨烯-吉西他滨前药纳米粒，并成功用于靶向不同的癌细胞系，从而提高了细胞摄取率和抗肿瘤效率，这标志着角鲨酰化方法衍生的首个靶向系统的诞生。
• VITAMIN C COMPLEXES
  申请人：CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE

  公开号：US20150045426A1

  公开（公告）日：2015-02-12

  A complex formed of at least one molecule of 5-(1,2-dihydroxy-ethyl)-3,4-dihydroxy-5H-furan-2-one or a derivative covalently bonded with at least one hydrocarbon radical with formula (A) as follows: wherein: •-m 1=1, 2, 3, 4, 5 or 6; •-m 2=0, 1, 2, 3, 4, 5 or 6; and represents the site of the bond with the molecule of 5-(1,2-dihydroxy-ethyl)-3,4-dihydroxy-5H-furan-2-one or derivative. Formula (I)

  至少包含一个分子5-(1,2-二羟基乙基)-3,4-二羟基-5H-呋喃-2-酮或其衍生物与至少一个具有以下式(A)的碳氢基团共价结合形成的复合物：其中： •-m1=1, 2, 3, 4, 5或6； •-m2=0, 1, 2, 3, 4, 5或6；并表示与5-(1,2-二羟基乙基)-3,4-二羟基-5H-呋喃-2-酮或其衍生物结合的位置。公式(I)
• [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。
• Trifluoromethyl ketones derived from squalene: inhibition of the cholesterol biosynthesis in HepG2 cells
  作者：Farid Benayoud、Ahmed Abouabdellah、Cyrille Richard、Danièle Bonnet-Delpon、Jean-Pierre Bégué、Danielle Levasseur、Olivier Boutaud、Francis Schuber

  DOI：10.1016/s0040-4039(00)01066-2

  日期：2000.8

  Trifluoromethyl ketones 1 and 2, have been prepared from trisnorsqualene aldehyde 3. These compounds and their corresponding alcohols 4 and 7 have been found to be good inhibitors of the biosynthesis of cholesterol in HepG2 cells. The inhibition is correlated with a decrease of the HMG-CoA reductase activity, probably resulting from the transformation of the fluorinated compounds into their corresponding oxysterols which could act as repressors of that enzyme. (C) 2000 Elsevier Science Ltd. All rights reserved.
• 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.