methyl di((9Z,12Z)-octadeca-9,12-dienyl)amine | 168681-38-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: methyl di((9Z,12Z)-octadeca-9,12-dienyl)amine
• 英文别名: (9Z,12Z)-N-methyl-N-[(9Z,12Z)-octadeca-9,12-dienyl]octadeca-9,12-dien-1-amine
• CAS: 168681-38-7
• 化学式: C₃₇H₆₉N
• 分子量: 527.962
• InChiKey: ZUVNJQGVJAFACY-QYCRHRGJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  14.7
• 重原子数：
  38
• 可旋转键数：
  30
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  亚麻醇 在 N-甲基咪唑 、 copper(l) iodide 、 2,2,6,6-四甲基哌啶氧化物 、 4,4'-二甲氧基-2,2'-联吡啶 、 氧气 、 tetramethylammonium triacetoxyborohydride 作用下， 以 N-甲基吡咯烷酮 、 甲醇 为溶剂， 40.0~100.0 ℃ 、800.01 kPa 条件下， 反应 0.59h， 生成 methyl di((9Z,12Z)-octadeca-9,12-dienyl)amine
  参考文献：
  名称：

  Continuous-Flow Synthesis of Cationic Lipid SST-01 via Safe and Scalable Aerobic Oxidation and Reductive Amination

  摘要：

  The synthesis of the cationic lipid SST-01, a key component of Kyowa Kirin's siRNA-lipid nanoparticles, through a two-step homogeneous continuous-flow process is described. Safe and scalable aerobic oxidation with a catalytic CuI/TEMPO system and diluted oxygen (5% O-2 in N-2) was utilized in the first step to provide a lipid aldehyde. Subsequent reductive amination of the first-step eluent with methylamine using tetramethylammonium triacetoxyborohydride provided the target SST-01 in an overall yield of 95%.

  DOI：

  10.1021/acs.oprd.0c00084

文献信息

• 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。
• Simplifying the Chemical Structure of Cationic Lipids for siRNA-Lipid Nanoparticles
  作者：Takeshi Kuboyama、Kaori Yagi、Tomoyuki Naoi、Tomohiro Era、Nobuhiro Yagi、Yoshisuke Nakasato、Hayato Yabuuchi、Saori Takahashi、Fumikazu Shinohara、Hiroto Iwai、Ayumi Koubara-Yamada、Kazumasa Hasegawa、Atsushi Miwa

  DOI：10.1021/acsmedchemlett.8b00652

  日期：2019.5.9

  report a potent cationic lipid, SST-02 ((3-hydroxylpropyl)dilinoleylamine), which possesses a simple chemical structure and is synthesized just in one step. Cationic lipids are key components of siRNA-lipid nanoparticles (LNP), which may serve as potential therapeutic agents for various diseases. For a decade, chemists have given enhanced potency and new functions to cationic lipids along with structural

  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。
• LIPID NANOPARTICLES FOR DRUG DELIVERY SYSTEM CONTAINING CATIONIC LIPIDS
  申请人：Kyowa Hakko Kirin Co., Ltd.

  公开号：EP2792367A1

  公开（公告）日：2014-10-22

  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: R1 and R2 are, the same or different, alkenyl, etc, and X3 is absent or is alkyl, etc, X1 and X2 are hydrogen atoms, or are combined together to form a single bond or alkylene, and Y1 is absent or anion, L1 is a single bond, etc, R3 is alkyl, etc), and the like.

  本发明提供了一种可将核酸轻松导入细胞的脂质纳米颗粒，它由式(I)代表的阳离子脂质组成 其中R1 和 R2 是相同或不同的烯基等，以及 X3 不存在或为烷基等、 X1 和 X2 为氢原子，或结合在一起形成单键或亚烷基，以及 Y1 不存在或为阴离子、 L1 是单键等、 R3为烷基等）等。