3-((3R,4R)-3,4-bis((9Z,12Z)-octadec-9,12-dienyloxy)pyrrolidin-1-yl)-N,N-dimethylpropanamide | 1346225-03-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3-((3R,4R)-3,4-bis((9Z,12Z)-octadec-9,12-dienyloxy)pyrrolidin-1-yl)-N,N-dimethylpropanamide
• 英文别名: 3-((3R,4R)-3,4-bis((9Z,12Z)-Octadec-9,12-dienyloxy)pyrrolidin-1-yl)-N,N-dimethyl propanamide；3-[(3R,4R)-3,4-bis[(9Z,12Z)-octadeca-9,12-dienoxy]pyrrolidin-1-yl]-N,N-dimethylpropanamide
• CAS: 1346225-03-3
• 化学式: C₄₅H₈₂N₂O₃
• 分子量: 699.158
• InChiKey: CPRXOCYNHXDWKI-QGFSRGMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  13.7
• 重原子数：
  50
• 可旋转键数：
  35
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  42
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (3R,4R)-3,4-bis((9Z,12Z)-octadec-9,12-dienyloxy)pyrrolidine 在 水 、 sodium ethanolate 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 氯仿 为溶剂， 反应 7.5h， 生成 3-((3R,4R)-3,4-bis((9Z,12Z)-octadec-9,12-dienyloxy)pyrrolidin-1-yl)-N,N-dimethylpropanamide
  参考文献：
  名称：

  CATIONIC LIPID

  摘要：

  本发明提供了一种阳离子脂质，其允许核酸轻松进入细胞，其表示为式(I)（其中：R1和R2为相同或不同的烯基等，X1和X2为氢原子，或结合在一起形成单键或烷基，X3不存在或为烷基等，Y不存在或为阴离子，a和b为相同或不同的0到3，L3为单键等，R3为烷基等，L1和L2为—O—，—CO—O—或—O—CO—），一种包含该阳离子脂质和核酸的组合物，以及一种通过使用包含该阳离子脂质和核酸的组合物将核酸引入细胞的方法，等等。

  公开号：

  US20130280305A1

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。
• Cationic lipid
  申请人：Kuboyama Takeshi

  公开号：US09408914B2

  公开（公告）日：2016-08-09

  The present invention provides a cationic lipid, which allow nucleic acids to be easily introduced into cells, represented by formula (I) (wherein: R1 and R2 are, the same or different, alkenyl, etc, and X1 and X2 are hydrogen atoms, or are combined together to form a single bond or alkylene, and X3 is absent or is alkyl, etc, Y is absent or anion, a and b are, the same or different, 0 to 3, and L3 is a single bond, etc, R3 is alkyl, etc, L1 and L2 are —O—, —CO—O— or —O—CO—), a composition comprising the cationic lipid and a nucleic acid, and a method for introducing a nucleic acid into a cell by using the composition comprising the cationic lipid and the nucleic acid, and the like.

  本发明提供了一种阳离子脂质，可以使核酸轻松地引入细胞中，其化学式表示为（I）（其中：R1和R2是相同或不同的烯基等，X1和X2是氢原子，或结合在一起形成单键或烷基，X3不存在或是烷基等，Y不存在或是阴离子，a和b是相同或不同的0到3，L3是单键等，R3是烷基等，L1和L2是-O-，-CO-O-或-O-CO-），以及包括该阳离子脂质和核酸的组合物，使用该组合物将核酸引入细胞中的方法等。
• 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-）。
• US9408914B2
  申请人：——

  公开号：US9408914B2

  公开（公告）日：2016-08-09
• US9845306B2
  申请人：——

  公开号：US9845306B2

  公开（公告）日：2017-12-19