2-methyl-2-dodecanoxycarbonylpropylene carbonate

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 2-methyl-2-dodecanoxycarbonylpropylene carbonate
• 英文别名: 2-methyldodecane oxycarbonylpropylene carbonate；Dodecyl 5-methyl-2-oxo-1,3-dioxane-5-carboxylate
• 化学式: C₁₈H₃₂O₅
• 分子量: 328.449
• InChiKey: QHTMNVZPJHSCSC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  23
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  苄基3-羟基-2-(羟基甲基)-2-甲基丙酸酯 在 吡啶 、 palladium 10% on activated carbon 、 氢气 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 氯仿 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， -78.0~20.0 ℃ 、275.8 kPa 条件下， 反应 22.0h， 生成 2-methyl-2-dodecanoxycarbonylpropylene carbonate
  参考文献：
  名称：

  EGFR-Targeted Polymeric Mixed Micelles Carrying Gemcitabine for Treating Pancreatic Cancer

  摘要：

  本研究的目的是设计GE11肽（YHWYGYTPQNVI）连接的聚乙烯醇-嵌段-聚（2-甲基-2-羧基-丙烯酸碳酸酯-gemcitabine-dodecanol）（PEG-b-PCC-g-GEM-g-DC）胶束，以增强吉西他滨（GEM）对EGFR阳性胰腺癌细胞的稳定性和靶向特异性。GE11-PEG-PCD/mPEG-b-PCC-g-GEM-g-DC混合胶束表现出EGFR依赖性增强的细胞摄取和细胞毒性，相较于经过随机化的肽HW12-PEG-PCD/mPEG-b-PCC-g-GEM-g-DC混合胶束和未修饰的mPEG-b-PCC-g-GEM-g-DC胶束。重要的是，GE11连接的混合胶束在全身给药后24小时内优先积累于原位胰腺肿瘤和肿瘤血管中。与HW12连接的混合胶束、未修饰的mPEG-b-PCC-g-GEM-g-DC胶束以及自由GEM配方相比，GE11连接的混合胶束抑制了原位胰腺肿瘤的生长。肿瘤生长抑制是通过肿瘤细胞和内皮细胞的凋亡介导的，具体通过免疫组织化学染色确定。总而言之，GE11连接的混合胶束是治疗EGFR过表达癌症的一种有前景的方法。

  DOI：

  10.1021/acs.biomac.5b01419

文献信息

• EGFR-Targeted Polymeric Mixed Micelles Carrying Gemcitabine for Treating Pancreatic Cancer
  作者：Goutam Mondal、Virender Kumar、Surendra K. Shukla、Pankaj K. Singh、Ram I. Mahato

  DOI：10.1021/acs.biomac.5b01419

  日期：2016.1.11

  The objective of this study was to design GE11 peptide (YHWYGYTPQNVI) linked micelles of poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylene carbonate-graft-gemcitabine-graft-dodecanol (PEG-b-PCC-g-GEM-g-DC) for enhanced stability and target specificity of gemcitabine (GEM) to EGFR-positive pancreatic cancer cells. GE11-PEG-PCD/mPEG-b-PCC-g-GEM-g-DC mixed micelles showed EGFR-dependent enhanced cellular uptake, and cytotoxicity as compared to scrambled peptide HW12-PEG-PCD/mPEG-b-PCC-g-GEM-g-DC mixed micelles and unmodified mPEG-b-PCC-g-GEM-g-DC micelles. Importantly, GE11-linked mixed micelles preferentially accumulated in orthotopic pancreatic tumor and tumor vasculature at 24 h post systemic administration. GE11-linked mixed micelles inhibited orthotopic pancreatic tumor growth compared to HW12-linked mixed micelles, unmodified mPEG-b-PCC-g-GEM-g-DC micelles, and free GEM formulations. Tumor growth inhibition was mediated by apoptosis of tumor cells and endothelial cells as determined by immunohistochemical staining. In summary, GE11-linked mixed micelles is a promising approach to treat EGFR overexpressing cancers.

  本研究的目的是设计GE11肽（YHWYGYTPQNVI）连接的聚乙烯醇-嵌段-聚（2-甲基-2-羧基-丙烯酸碳酸酯-gemcitabine-dodecanol）（PEG-b-PCC-g-GEM-g-DC）胶束，以增强吉西他滨（GEM）对EGFR阳性胰腺癌细胞的稳定性和靶向特异性。GE11-PEG-PCD/mPEG-b-PCC-g-GEM-g-DC混合胶束表现出EGFR依赖性增强的细胞摄取和细胞毒性，相较于经过随机化的肽HW12-PEG-PCD/mPEG-b-PCC-g-GEM-g-DC混合胶束和未修饰的mPEG-b-PCC-g-GEM-g-DC胶束。重要的是，GE11连接的混合胶束在全身给药后24小时内优先积累于原位胰腺肿瘤和肿瘤血管中。与HW12连接的混合胶束、未修饰的mPEG-b-PCC-g-GEM-g-DC胶束以及自由GEM配方相比，GE11连接的混合胶束抑制了原位胰腺肿瘤的生长。肿瘤生长抑制是通过肿瘤细胞和内皮细胞的凋亡介导的，具体通过免疫组织化学染色确定。总而言之，GE11连接的混合胶束是治疗EGFR过表达癌症的一种有前景的方法。
• ANTIMICROBIAL POLYMERS AND METHODS OF MANUFACTURE THEREOF
  申请人：HEDRICK James

  公开号：US20110150977A1

  公开（公告）日：2011-06-23

  Biodegradable cationic block copolymers are disclosed, comprising a hydrophilic block comprising first repeat units derived from a first cyclic carbonyl monomer by ring-opening polymerization, wherein more than 0% of the first repeat units comprise a side chain moiety comprising a quaternary amine group; a hydrophobic block comprising second repeat units derived from a second cyclic carbonyl monomer by ring-opening polymerization; an optional endcap group; and a chain fragment derived from an initiator for the ring opening polymerization. The cationic block copolymers form aqueous micelle mixtures suitable for antimicrobial applications.

  披露了可生物降解的阳离子嵌段共聚物，包括由第一环状羰基单体通过环开聚合得到的第一重复单元构成的亲水性嵌段，其中超过0%的第一重复单元包含一个侧链基团，该侧链基团包含一个季铵盐基团；包括由第二环状羰基单体通过环开聚合得到的第二重复单元构成的疏水性嵌段；一个可选的端基团；以及由环开聚合引发剂导致的链片段。这些阳离子嵌段共聚物形成适用于抗菌应用的水胶胶束混合物。
• Pharmacokinetics and Biodistribution of GDC-0449 Loaded Micelles in Normal and Liver Fibrotic Mice
  作者：Rinku Dutta、Virender Kumar、Yang Peng、Ruby E. Evande、Jean L. Grem、Ram I. Mahato

  DOI：10.1007/s11095-016-2081-3

  日期：2017.3

  To determine the pharmacokinetic parameters and biodistribution of GDC-0449 loaded polymeric micelles after systemic administration into common bile duct ligation (CBDL) induced liver fibrotic mice. We used GDC-0449 encapsulated methoxy poly (ethylene glycol)-block-poly (2-methyl-2-carboxyl-propylene carbonate)-graft-dodecanol (PEG-PCD) non-targeted polymeric micelles for GDC-0449 delivery to normal and liver fibrotic mice. To maximize GDC-0449 delivery to hepatic stellate cells (HSCs), mixed micelles formulations with 10, 20 and 30% w/w mannose-6-phosphate (M6P)-conjugated micelles were administered to normal and liver fibrotic mice for targeting M6P/IGF-IIR overexpressed on activated HSCs and biodistribution of GDC-0449 was determined at 30 and 120 min post systemic administration. GDC-0449 distributed to all major organs after systemic administration of drug loaded micelles, with higher accumulation in the liver of both normal and fibrotic mice. The plasma concentration versus time profiles suggest rapid clearance of GDC-0449 after systemic administration of drug loaded micelles in both normal and fibrotic mice, with similar plasma clearance (CL), area under the curve (AUCint) and volume of distribution at steady state (Vss). However, there is significant increase in GDC-0449 accumulation in the liver when M6P-conjugated mixed micelles were injected, with the highest GDC-0449 concentration in the liver with mixed micelles carrying 30% M6P-conjugated polymer. HSCs accounted for 14.19% of GDC-0449 accumulation for M6P-targeted micelles in fibrotic mice compared to 5.62% of non-targeted micelles in the liver uptake study. M6P-conjugated GDC-0449 loaded mixed micelles may be used as a potential drug delivery vehicle for treating liver fibrosis.

  为了确定 GDC-0449 负载聚合物胶束在胆总管结扎（CBDL）诱导的肝纤维化小鼠全身给药后的药代动力学参数和生物分布。我们使用GDC-0449包封甲氧基聚（乙二醇）-块-聚（2-甲基-2-羧基-碳酸丙烯酯）-接枝-十二醇（PEG-PCD）非靶向聚合物胶束向正常小鼠和肝纤维化小鼠递送GDC-0449。为了最大限度地将GDC-0449输送到肝星状细胞（HSCs），给正常小鼠和肝纤维化小鼠注射了含10%、20%和30% w/w 6-磷酸甘露糖（M6P）共轭胶束的混合胶束制剂，以靶向活化的HSCs上过表达的M6P/IGF-IIR，并在全身给药后30分钟和120分钟测定了GDC-0449的生物分布。全身给药胶束后，GDC-0449分布到所有主要器官，在正常小鼠和纤维化小鼠的肝脏中积累较多。血浆浓度随时间的变化曲线表明，正常小鼠和纤维化小鼠全身给药后，GDC-0449会迅速清除，血浆清除率（CL）、曲线下面积（AUCint）和稳态分布容积（Vss）相似。然而，当注射M6P共轭混合胶束时，肝脏中的GDC-0449蓄积量明显增加，在含有30%M6P共轭聚合物的混合胶束中，肝脏中的GDC-0449浓度最高。在肝脏吸收研究中，M6P靶向胶束在纤维化小鼠体内的GDC-0449累积量占造血干细胞的14.19%，而非靶向胶束仅占5.62%。负载 M6P 的 GDC-0449 混合胶束可用作治疗肝纤维化的潜在给药载体。
• [EN] AMPHIPATHIC CO-OLIGOMERS FOR THE DELIVERY OF SIRNA<br/>[FR] CO-OLIGOMÈRES AMPHIPATHIQUES POUR ADMINISTRATION D'ARNSI
  申请人：UNIV LELAND STANFORD JUNIOR

  公开号：WO2013036532A1

  公开（公告）日：2013-03-14

  Co-oligomer compounds, complexes of the same with polyanions, such as siRNAs, and methods for using the same are provided. the delivery of polynucleotides, into a cell. The subject co-oligomers include at least a liphopilic monomer and at least a hydrophilic monomer (e.g., a guanidinium containing monomer). In some embodiments, the co-oligomer compounds are capable of complexing a siRNA of interest, thereby increasing the cell permeability of the siRNA, prior to release of the siRNA into the cell. In some embodiments, the subject method is a method of delivery a siRNA into a cell. In some embodiments, the subject method is a method of reducing expression of a protein target of a siRNA of interest. The subject co-oligomer / siRNA complexes may be formulated and administered to a subject to treat a condition resulting from expression of a protein target of the siRNA of interest.

  本文提供了共聚物化合物、与聚阴离子（如siRNA）形成的复合物以及使用它们的方法。这些化合物可用于将多核苷酸递送到细胞内。该共聚物包含至少一个亲脂性单体和至少一个亲水性单体（例如含有鸟氨酸单体）。在某些实施例中，共聚物化合物能够与感兴趣的siRNA形成复合物，从而增加siRNA的细胞渗透性，然后将siRNA释放到细胞中。在某些实施例中，该方法是将siRNA递送到细胞的方法。在某些实施例中，该方法是减少感兴趣的siRNA的蛋白质靶标表达的方法。该共聚物/siRNA复合物可以制备并用于治疗由感兴趣的siRNA的蛋白质靶标表达引起的疾病。
• Hydrogel Compositions and Methods of Preparation Thereof
  申请人：Fukushima Kazuki

  公开号：US20110054064A1

  公开（公告）日：2011-03-03

  A block copolymer includes a hydrophobic block and a hydrophilic block, wherein the hydrophobic block and the hydrophilic block include repeating units derived from ring opening polymerization of one or more cyclic carbonate monomers. The one or more cyclic carbonate monomers are independently selected from compounds of the general formula (II): wherein each Q′ and Q a group independently represents a hydrogen, an alkyl group, a halide, a carboxy group, an ester group, an amide group, an aryl group, an alkoxy group, or a foregoing Q′ or Q a group substituted with a carboxy group or an ester group, at least one Q′ and Q a group includes an ester group; each Y independently represents O, S, NH, or NQ″; n is an integer from 0 to 6, wherein when n is 0, carbons labeled 4 and 6 are linked together by a single bond; each Q″ group independently represents an alkyl group, an aryl group, or a foregoing Q″ group substituted with a carboxy group, or an ester group.

  一种嵌段共聚物包括一个亲疏水性嵌段，其中该亲疏水性嵌段包括由一个或多个环状碳酸酯单体的开环聚合所得的重复单元。该一个或多个环状碳酸酯单体是从通式（II）的化合物中独立选择的，其中每个Q'和Qa独立地表示氢、烷基、卤素、羧基、酯基、酰胺基、芳基、烷氧基或者前述被羧基或酯基取代的Q'或Qa基团，至少一个Q'和Qa基团包括一个酯基；每个Y独立地表示O、S、NH或NQ"；n是从0到6的整数，当n为0时，被标记为4和6的碳通过单键连接在一起；每个Q"基团独立地表示烷基、芳基或者前述被羧基或酯基取代的Q"基团。