2-aminoethyl n-hexadecyl ether | 460343-15-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-aminoethyl n-hexadecyl ether
• 英文别名: (2-n-Hexadecyloxyethyl)amin；2-(Hexadecyloxy)Ethanamine；2-hexadecoxyethanamine
• CAS: 460343-15-1
• 化学式: C₁₈H₃₉NO
• 分子量: 285.514
• InChiKey: FWFOSYLRRIGGHS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  20
• 可旋转键数：
  17
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-aminoethyl n-hexadecyl ether 在 sodium hydroxide 、 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 80.0h， 生成 N,N-di[2-n-hexadecyloxyethyl]-N,N-di[2-hydroxyethyl]ammonium chloride
  参考文献：
  名称：

  Anchor Dependency for Non-Glycerol Based Cationic Lipofectins: Mixed Bag of Regular and Anomalous Transfection Profiles

  摘要：

  Although detailed structure activity, physicochemical and biophysical investigations in probing the anchor influence in liposomal gene delivery have been reported for glycerol-based transfection lipids, the corresponding investigation for non-glycerol based simple monocationic transfection lipids have not yet been undertaken. Towards this end, herein, we delineate our structure - activity and physicochemical approach in deciphering the anchor dependency in liposomal gene delivery using fifteen new structural analogues (lipids 1 - 15) of recently reported nonglycerol based monocationic transfection lipids. The C-14 analogues in both series 1 (lipids 1 - 6) and series 2 (lipids 7-15) showed maximum efficiency in transfecting COS-1 and CHO cells. However, the C-12 analogue of the ether series (lipid 3) exhibited a seemingly anomalous behavior compared with its transfection efficient C-10 and C-14 analogues (lipids 2 and 4) in being completely inefficient to transfect both COS-1 and CHO cells. The present structure - activity investigation also convincingly demonstrates that enhancement of transfection efficiencies through incorporation of membrane reorganizing unsaturation elements in the hydrophobic anchor of cationic lipids is not universal but cell dependent. The strength of the interaction of lipids 1 - 15 with DNA was assessed by their ability to exclude ethidium bromide bound to the DNA. Cationic lipids with long hydrophobic tails were found, in general, to be efficient in excluding EtBr from DNA. Gel to liquid crystalline transition temperatures of the lipids was measured by fluorescence anisotropy measurement technique. In general (lipid 2 being an exception), transfection efficient lipids were found to have their mid transition temperatures at or below physiological temperatures (37degreesC).

  DOI：

  10.1002/1521-3765(20020215)8:4<900::aid-chem900>3.0.co;2-x
• 作为产物：
  描述：

  α-氢化-ω-羟基异十六烷醇聚(氧-1,2-乙烷二基) 在 叠氮磷酸二苯酯 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三苯基膦 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 31.17h， 生成 2-aminoethyl n-hexadecyl ether
  参考文献：
  名称：

  Lipophilic amines as potent inhibitors of N-acylethanolamine-hydrolyzing acid amidase

  摘要：

  N-Acylethanolamines (NAEs) including N-arachidonoylethanolamine (anandamide) and N-palmitoylethanolamine are endogenous lipid mediators. These molecules are degraded to the corresponding fatty acids and ethanolamine by fatty acid amide hydrolase (FAAH) or NAE-hydrolyzing acid amidase (NAAA). Lipophilic amines, especially pentadecylamine (2c) and tridecyl 2-aminoacetate (11b), were found to exhibit potent NAAA inhibitory activities (IC50 = 5.7 and 11.8 mu M), with much weaker effects on FAAH. These simple structures would provide a scaffold for further improvement in NAAA inhibitory activity. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.03.065

文献信息

• [EN] DI- AND TRI-CATIONIC GLYCOSYLATED ANTITUMOR ETHER LIPIDS, L-GUCOSYLATED GAELS AND RHAMNOSE-LINKED GAELS AS CYTOTOXIC AGENTS AGAINST EPITHELIAL CANCER CELLS AND CANCER STEM CELLS<br/>[FR] ETHERS LIPIDIQUES ANTITUMORAUX GLYCOSYLÉS DI- ET TRICATIONIQUES, GAEL L-GLYCOSYLÉS ET GAEL LIÉS À DU RHAMNOSE UTILISABLES EN TANT QU'AGENTS CYTOTOXIQUES DIRIGÉS CONTRE DES CELLULES ÉPITHÉLIALES CANCÉREUSES ET DES CELLULES SOUCHES CANCÉREUSES
  申请人：UNIV MANITOBA

  公开号：WO2015179983A1

  公开（公告）日：2015-12-03

  Glycosylated Antitumor Ether Lipids (GAELs) kill cancer cells by a nonapoptotic pathway which is an attractive strategy to avoid resistance. To further optimize the antitumor effect, we prepared various analogs of di-, and tri-cationic GAEL analogs differing in the nature of the sugar (D-giucose or L-glucose), the anomeric linkage as well as position of the glycerolipid moiety. The di- and tri-cationic GAELs were synthesized and their in vitro anticancer properties were evaluated against drug resistant and aggressively growing cancer cell lines derived from human breast, prostate, pancreatic and ovarian cancers. The most potent dicationic GAEL analogs were also studied against cancer stem cells obtained from breast BT 474, prostate DU145 and ovarian A2780cp cell lines. Our results indicate that the number of positive charges, the position of the amino substituents and the nature of the sugar have significant effects on the anticancer activities of these compounds. The most active analog kill 50% of the cells at concentration range of 0.5-5μΜ and 90% of the cells at the concentration of 1-10μΜ depending on type of cancer cells.

  糖基化抗肿瘤醚脂质（GAELs）通过一种非凋亡途径杀灭癌细胞，这是一种吸引人的策略，可以避免抗药性。为了进一步优化抗肿瘤效果，我们制备了不同的双-和三-阳离子GAEL类似物，其糖的性质（D-葡萄糖或L-葡萄糖）、缩醛键以及甘油脂类团的位置不同。合成了双-和三-阳离子GAEL类似物，并评估了它们对人类乳腺、前列腺、胰腺和卵巢癌衍生的耐药和快速生长的癌细胞系的体外抗癌性能。最有效的双阳离子GAEL类似物也针对从乳腺BT 474、前列腺DU145和卵巢A2780cp细胞系中获得的癌干细胞进行了研究。我们的结果表明，阳离子数量、氨基取代物的位置和糖的性质对这些化合物的抗癌活性有显著影响。最活跃的类似物在浓度范围为0.5-5μΜ时杀死50%的细胞，在浓度为1-10μΜ时杀死90%的细胞，具体取决于癌细胞类型。
• PRODUCTION OF A COMPOSITION CONTAINING A COMPLEX BETWEEN A MEMBRANE COMPOSED OF A LIPID MONOLAYER AND A NUCLEIC ACID, AND, A LIPID MEMBRANE FOR ENCAPSULATING THE COMPLEX THEREIN
  申请人：Kyowa Hakko Kirin Co., Ltd.

  公开号：EP3301086A1

  公开（公告）日：2018-04-04

  The present invention relates to a method for producing a composition containing a complex between a membrane composed of a lipid monolayer (reversed micelle) and a nucleic acid, and a lipid membrane for encapsulating the complex therein, comprising the following steps A to D: Step A: preparing a complex between the nucleic acid and a liposome comprising a cationic lipid represented by the formula (I) and/or a cationic lipid other than cationic lipid represented by the formula (I); Step B: preparing a dispersion liquid by dispersing the complex in water or ethanol aqueous solution; Step C: preparing a solution by dissolving the formula (I) and/or the cationic lipid other than cationic lipid represented by the formula (I) in ethanol or an ethanol aqueous solution; and Step D: mixing the dispersion liquid and the solution, and optionally adding water; wherein the formula (I) is (wherein: R1 and R2 are, the same or different, each linear or branched alkyl, alkenyl or alkynyl having 12 to 24 carbon atoms, X1 and X2 are hydrogen atoms, or are combined together to form a single bond or alkylene, X3 is absent or is alkyl having 1 to 6 carbon atoms, or alkenyl having 3 to 6 carbon atoms, when X3 is absent, Y is absent, a and b are 0, L3 is a single bond, R3 is alkyl having 1 to 6 carbon atoms, alkenyl having 3 to 6 carbon atoms, or alkyl having 1 to 6 carbon atoms or alkenyl having 3 to 6 carbon atoms substituted with 1 to 3 substituent(s), which is(are), the same or different, amino, monoalkylamino, dialkylamino, trialkylammonio, hydroxy, alkoxy, carbamoyl, monoalkylcarbamoyl, or dialkylcarbamoyl, and L1 and L2 are -O-, Y is absent, a and b are, the same or different, 0 to 3, and are not 0 at the same time, L3 is a single bond, R3 is alkyl having 1 to 6 carbon atoms, alkenyl having 3 to 6 carbon atoms, or alkyl having 1 to 6 carbon atoms or alkenyl having 3 to 6 carbon atoms substituted with 1 to 3 substituent(s), which is(are), the same or different, amino, monoalkylamino, dialkylamino, trialkylammonio, hydroxy, alkoxy, carbamoyl, monoalkylcarbamoyl, or dialkylcarbamoyl, L1 and L2 are, the same or different, -O-, -CO-O- or -O-CO-, Y is absent, a and b are, the same or different, 0 to 3, L3 is a single bond, R3 is a hydrogen atom, and L1 and L2 are, the same or different, -O-, -CO-O- or -O-CO-, or Y is absent, a and b are, the same or different, 0 to 3, L3 is -CO- or -CO-O-, R3 is alkyl having 1 to 6 carbon atoms or alkenyl having 3 to 6 carbon atoms substituted with 1 to 3 substituent(s), which is(are), the same or different, amino, monoalkylamino, dialkylamino, trialkylammonio, hydroxy, alkoxy, carbamoyl, monoalkylcarbamoyl, or dialkylcarbamoyl, wherein at least one of the substituents is amino, monoalkylamino, dialkylamino, or trialkylammonio, and L1 and L2 are , the same or different, -O-, -CO-O- or -O-CO-, and when X3 is alkyl having 1 to 6 carbon atoms or alkenyl having 3 to 6 carbon atoms, Y is a pharmaceutically acceptable anion, a and b are, the same or different, 0 to 3, L3 is a single bond, R3 is alkyl having 1 to 6 carbon atoms, alkenyl having 3 to 6 carbon atoms, L1 and L2 are, the same or different, -O-, -CO-O- or -O-CO-).

  本发明涉及一种生产含有由脂质单层（反向胶束）组成的膜与核酸之间的复合物的组合物以及用于将复合物包封在其中的脂质膜的方法，包括以下步骤A至D： 步骤 A：制备核酸与由式（I）代表的阳离子脂质和/或除式（I）代表的阳离子脂质以外的阳离子脂质组成的脂质体之间的复合物； 步骤 B：将复合物分散于水或乙醇水溶液中，制备分散液； 步骤 C：将式（I）和/或式（I）代表的阳离子脂质以外的阳离子脂质溶解在乙醇或乙醇水溶液中，制备溶液；以及 步骤 D：混合分散液和溶液，可选择加水； 其中式 (I) 为 (其中 R1 和 R2 相同或不同，各自为具有 12 至 24 个碳原子的直链或支链烷基、烯基或炔基、 X1 和 X2 为氢原子，或结合在一起形成单键或亚烷基、 X3 不存在或为具有 1 至 6 个碳原子的烷基或具有 3 至 6 个碳原子的烯基、 当 X3 不存在时 Y 不存在，a 和 b 为 0，L3 为单键，R3 为具有 1 至 6 个碳原子的烷基、具有 3 至 6 个碳原子的烯基、或具有 1 至 6 个碳原子的烷基或具有 3 至 6 个碳原子的烯基，这些取代基相同或不同，为氨基、单烷基氨基、二烷基氨基、三烷基氨基、羟基、烷氧基、氨基甲酰基、单烷基氨基甲酰基或二烷基氨基甲酰基，且 L1 和 L2 为 -O-、 Y 不存在，a 和 b 相同或不同，为 0 至 3，且同时不为 0，L3 为单键，R3 为具有 1 至 6 个碳原子的烷基、具有 3 至 6 个碳原子的烯基，或具有 1 至 6 个碳原子的烷基或具有 3 至 6 个碳原子的烯基被 1 至 3 个取代基取代、L1和L2是相同或不同的氨基、单烷基氨基、二烷基氨基、三烷基氨基、羟基、烷氧基、氨基甲酰基、单烷基氨基甲酰基或二烷基氨基甲酰基，-O-、-CO-O-或-O-CO-、 Y 不存在，a 和 b 是相同或不同的 0 至 3，L3 是单键，R3 是氢原子，L1 和 L2 是相同或不同的 -O-、-CO-O- 或 -O-CO-，或 羟基、烷氧基、氨基甲酰基、单烷基氨基甲酰基或二烷基氨基甲酰基，其中至少一个取代基是氨基、单烷基氨基、二烷基氨基或三烷基氨基，且 L1 和 L2 是相同或不同的 -O-、-CO-O- 或 -O-CO-，以及 当 X3 是具有 1 至 6 个碳原子的烷基或具有 3 至 6 个碳原子的烯基时，Y 是药学上可接受的阴离子，a 和 b 是相同或不同的 0 至 3，L3 是单键，R3 是具有 1 至 6 个碳原子的烷基或具有 3 至 6 个碳原子的烯基，L1 和 L2 是相同或不同的-O-、-CO-O-或-O-CO-）。
• COMB-SHAPED DIOL, WATER-SOLUBLE POLYURETHANE, AND USE THEREOF
  申请人：Mitsui Chemicals, Inc.

  公开号：EP1184364B1

  公开（公告）日：2010-07-28
• PREVENTION AND TREATMENT OF INFLAMMATORY CONDITIONS
  申请人：GRI Bio, Inc.

  公开号：EP3229811B1

  公开（公告）日：2021-02-24
• DI- and Tri-Cationic Glycosylated Antitumor Ether Lipids, L-Gucosylated Gaels and Rhamnose-Linked Gaels as Cytotoxic Agents Against Epithelial Cancer Cells and Cancer Stem Cells
  申请人：The University of Manitoba

  公开号：US20170189438A1

  公开（公告）日：2017-07-06

  Glycosylated Antitumor Ether Lipids (GAELs) kill cancer cells by a nonapoptotic pathway which is an attractive strategy to avoid resistance. To further optimize the antitumor effect, we prepared various analogs of di-, and tri-cationic GAEL analogs differing in the nature of the sugar (D-giucose or L-glucose), the anomeric linkage as well as position of the glycerolipid moiety. The di- and tri-cationic GAELs were synthesized and their in vitro anticancer properties were evaluated against drug resistant and aggressively growing cancer cell lines derived from human breast, prostate, pancreatic and ovarian cancers. The most potent dicationic GAEL analogs were also studied against cancer stem cells obtained from breast BT 474, prostate DU145 and ovarian A2780cp cell lines. Our results indicate that the number of positive charges, the position of the amino substituents and the nature of the sugar have significant effects on the anticancer activities of these compounds. The most active analog kill 50% of the cells at concentration range of 0.5-5 μM and 90% of the cells at the concentration of 1-10 μM depending on type of cancer cells.