(9Z)-N-(9Z)-9-十八碳烯-1-基-9-十八碳烯-1-胺 | 40165-68-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: (9Z)-N-(9Z)-9-十八碳烯-1-基-9-十八碳烯-1-胺
• 中文别名: 双油基胺；二醇eyl胺
• 英文名称: di((Z)-octadec-9-enyl)amine
• 英文别名: Dioleylamine；(Z)-N-[(Z)-octadec-9-enyl]octadec-9-en-1-amine
• CAS: 40165-68-2
• 化学式: C₃₆H₇₁N
• 分子量: 517.966
• InChiKey: JTQQDDNCCLCMER-CLFAGFIQSA-N

物化性质

• 沸点：
  590.6±39.0 °C(Predicted)
• 密度：
  0.837±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  15.6
• 重原子数：
  37
• 可旋转键数：
  32
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  1

安全信息

• 海关编码：
  2921199090

反应信息

• 作为反应物：
  描述：

  (9Z)-N-(9Z)-9-十八碳烯-1-基-9-十八碳烯-1-胺 在 lithium aluminium tetrahydride 、 sodium ethanolate 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 6.0h， 生成 C₃₉H₇₇NO
  参考文献：
  名称：

  简化用于siRNA-脂质纳米颗粒的阳离子脂质的化学结构。

  摘要：

  我们报告了有效的阳离子脂质，SST-02（（3-羟丙基）二亚油胺），具有简单的化学结构，并且仅一步就合成了。阳离子脂质是siRNA-脂质纳米颗粒（LNP）的关键成分，可作为各种疾病的潜在治疗剂。十年来，化学家赋予阳离子脂质增强的功效和新功能以及结构复杂性。在这项研究中，我们进行了化学简单的药用化学研究，发现甚至二亚油基甲胺（SST-01）和甲基棕榈油胺也可以用于体内和体外siRNA递送。进一步的优化表明，羟基增强了效能，SST-02在VII因子（FVII）模型中显示的ID50为0.02 mg / kg。给予3 mg / kg SST-02 LNP的大鼠体重，血液化学或血液学参数无变化，而AST水平在5 mg / kg剂量下降低。SST-02的使用避免了冗长的合成路线，因此可以降低核酸治疗剂的未来成本。

  DOI：

  10.1021/acsmedchemlett.8b00652
• 作为产物：
  描述：

  油醇 在 sodium tetrahydroborate 、 Celite 、 magnesium sulfate 、 pyridinium chlorochromate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 8.0h， 生成 (9Z)-N-(9Z)-9-十八碳烯-1-基-9-十八碳烯-1-胺
  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

文献信息

• Design of Ionizable Lipids To Overcome the Limiting Step of Endosomal Escape: Application in the Intracellular Delivery of mRNA, DNA, and siRNA
  作者：Damien Habrant、Pauline Peuziat、Thibault Colombani、Laurence Dallet、Johan Gehin、Emilie Goudeau、Bérangère Evrard、Olivier Lambert、Thomas Haudebourg、Bruno Pitard

  DOI：10.1021/acs.jmedchem.5b01679

  日期：2016.4.14

  The intracellular delivery of nucleic acid molecules is a complex process involving several distinct steps; among these the endosomal escape appeared to be of particular importance for an efficient protein production (or inhibition) into host cells. In the present study, a new series of ionizable vectors, derived from naturally occurring aminoglycoside tobramycin, was prepared using improved synthetic

  核酸分子的细胞内递送是一个复杂的过程，涉及几个不同的步骤。其中，对于有效地向宿主细胞中产生蛋白质（或抑制），内体逃逸似乎尤为重要。在本研究中，使用改良的合成程序制备了一系列新的可离子化的载体，这些载体均来自天然存在的氨基糖苷妥布霉素，可在接头和疏水域上进行结构变化。新的可电离脂质与mRNA，DNA或siRNA之间形成的复合物通过冷冻TEM实验进行了表征，并使用不同的细胞类型评估了它们的转染能力。我们证明了铅分子30，带有可生物降解的二酯连接子，与核酸形成小的复合物，并且对所有测试的核酸和细胞类型均具有非常高的转染效率。获得的结果表明，通过脂质混合机制优化的内体逃逸，可改善30种“通用”递送特性。
• CATIONIC LIPID
  申请人：Kyowa Hakko Kirin Co., Ltd.

  公开号：US20140294978A1

  公开（公告）日：2014-10-02

  The present invention provides a cationic lipid and the like. The cationic lipid is for delivering a medicament containing a cationic lipid which facilitates the introduction of a nucleic acid into a cell or the like, and is represented by formula (I). In the formula, R 1 is linear or branched alkyl, alkenyl, or alkynyl, each having 8 to 24 carbon atoms, R 2 is linear or branched alkyl, alkenyl, or alkynyl, each having 8 to 24 carbon atoms, or alkoxyethylene, alkoxypropylene, alkenyloxyethylene, alkenyloxypropylene, alkynyloxyethylene, or alkynyloxypropylene, R 3 and R 4 may be the same or different, and are each alkyl having 1 to 3 carbon atoms or are combined together to form alkylene having 2 to 6 carbon atoms, or R 3 and R 5 are combined together to form alkylene having 2 to 6 carbon atoms, R 5 is a hydrogen atom, alkyl having 1 to 6 carbon atoms, alkenyl having 3 to 6 carbon atoms, amino, monoalkylamino, hydroxy, alkoxy, carbamoyl, monoalkylcarbamoyl, dialkylcarbamoyl, or the like, or is combined together with R 3 to form alkylene having 2 to 6 carbon atoms, X is alkylene having 1 to 6 carbon atoms, and Y is a single bond, alkylene having 1 to 6 carbon atoms, or the like.

  本发明提供了一种阳离子脂质等。该阳离子脂质用于传递含有阳离子脂质的药物，有助于将核酸引入细胞或类似物中，并由式(I)表示。在该式中，R1为具有8到24个碳原子的线性或支链烷基、烯基或炔基，R2为具有8到24个碳原子的线性或支链烷基、烯基或炔基，或者为烷氧乙烯、烷氧丙烯、烯氧乙烯、烯氧丙烯、炔氧乙烯或炔氧丙烯，R3和R4可以相同也可以不同，分别为具有1到3个碳原子的烷基，或者结合在一起形成具有2到6个碳原子的烷基，或者R3和R5结合在一起形成具有2到6个碳原子的烷基，R5为氢原子、具有1到6个碳原子的烷基、具有3到6个碳原子的烯基、氨基、单烷基氨基、羟基、烷氧基、氨基甲酰基、单烷基氨基甲酰基、二烷基氨基甲酰基等，或者与R3结合在一起形成具有2到6个碳原子的烷基，X为具有1到6个碳原子的烷基，Y为单键、具有1到6个碳原子的烷基等。
• LIPID NANO PARTICLES COMPRISING COMBINATION OF CATIONIC LIPID
  申请人：KYOWA HAKKO KIRIN CO., LTD.

  公开号：US20140045913A1

  公开（公告）日：2014-02-13

  The present invention provides a lipid nano-particles, which allow nucleic acids to be easily introduced into cells, comprising a cationic lipid represented by formula (I) (wherein: R 1 and R 2 are, the same or different, alkenyl, etc, and X 3 is absent or is alkyl, etc, X 1 and X 2 are hydrogen atoms, or are combined together to form a single bond or alkylene, and Y 1 is absent or anion, L 1 is a single bond, etc, R 3 is alkyl, etc), and a cationic lipid represented by formula (II) (wherein: R 4 and R 5 are, the same or different, alkenyl, etc, and X 4 and X 5 are hydrogen atoms, or are combined together to form a single bond or alkylene, and X 6 is absent or is alkyl, etc, Y 2 is absent or anion, a and b are, the same or different, 0 to 3, and L 4 is a single bond, etc, R 6 is alkyl, etc, L 2 and L 3 are —O—, —CO—O— or —O—CO—), and the like.

  本发明提供了一种脂质纳米粒子，可以使核酸轻松地进入细胞，包括由式(I)表示的阳离子脂质（其中：R1和R2是相同或不同的烯基等，X3不存在或是烷基等，X1和X2是氢原子，或结合在一起形成单键或亚烷基，Y1不存在或是阴离子，L1是单键等，R3是烷基等），以及由式(II)表示的阳离子脂质（其中：R4和R5是相同或不同的烯基等，X4和X5是氢原子，或结合在一起形成单键或亚烷基，X6不存在或是烷基等，Y2不存在或是阴离子，a和b是相同或不同的0到3，L4是单键等，R6是烷基等，L2和L3是—O—，—CO—O—或—O—CO—）等。
• LIPID NANO PARTICLES COMPRISING CATIONIC LIPID FOR DRUG DELIVERY SYSTEM
  申请人：Kyowa Hakko Kirin Co., Ltd.

  公开号：US20140039032A1

  公开（公告）日：2014-02-06

  The present invention provides a lipid nano-particles, which allow nucleic acids to be easily introduced into cells, comprising a cationic lipid represented by formula (I) (wherein: R 1 and R 2 are, the same or different, alkenyl, etc, and X 3 is absent or is alkyl, etc, X 1 and X 2 are hydrogen atoms, or are combined together to form a single bond or alkylene, and Y 1 is absent or anion, L 1 is a single bond, etc, R 3 is alkyl, etc), and the like.

  本发明提供了一种脂质纳米粒子，允许核酸轻松地被引入细胞中，包括由式(I)表示的阳离子脂质（其中：R1和R2是相同或不同的烯基等，X3不存在或是烷基等，X1和X2是氢原子，或结合在一起形成单键或亚烷基，Y1不存在或是阴离子，L1是单键等，R3是烷基等），等等。
• RNAi PHARMACEUTICAL COMPOSITION FOR SUPPRESSING EXPRESSION OF KRAS GENE
  申请人：Kyowa Hakko Kirin Co., Ltd.

  公开号：US20140044755A1

  公开（公告）日：2014-02-13

  The present invention provides a composition for suppressing the expression of a KRAS gene, comprising a lipid particle containing, as a drug, a double-stranded nucleic acid having an antisense strand having a sequence of bases complementary to the sequence of at least 19 continuous bases of any one KRAS gene's mRNA of sequence Nos. 1 to 3; and a cationic lipid represented by the following formula (I): wherein R 1 and R 2 , which are the same or different, are each linear or branched alkyl, alkenyl or alkynyl having a carbon number of from 12 to 24; L 1 and L 2 , which are the same or different, are each —CO—O— or —O—CO—; a and b, which are the same or different, are each 1 to 3; and R 3 is a hydrogen atom, alkyl having a carbon number of from 1 to 6, or alkenyl having a carbon number of from 3 to 6, and the like.

  本发明提供了一种用于抑制KRAS基因表达的组合物，包括含有脂质颗粒的药物，该药物是具有与序列号为1至3的任一KRAS基因的mRNA的至少19个连续碱基序列互补的反义链的双链核酸；以及由以下式（I）表示的阳离子脂质： 其中 R1和R2，相同或不同，分别是线性或支链烷基，烯基或炔基，碳数为12至24； L1和L2，相同或不同，分别是—CO—O—或—O—CO—； a和b，相同或不同，分别为1至3； R3是氢原子，碳数为1至6的烷基，或碳数为3至6的烯基等。