N,N-dimethyl-3,4-bis((9Z,12Z)-octadeca-9,12-dien-1-yloxy)butan-1-amine | 1192257-55-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N,N-dimethyl-3,4-bis((9Z,12Z)-octadeca-9,12-dien-1-yloxy)butan-1-amine
• 英文别名: N,N-dimethyl-3,4-bis[(9Z,12Z)-octadeca-9,12-dienyloxy]butan-1-amine；1,2-dilinoleyloxy-(N,N-dimethyl)-butyl-4-amine；N,N-dimethyl-3,4-bis[(9Z,12Z)-octadeca-9,12-dienoxy]butan-1-amine
• CAS: 1192257-55-8
• 化学式: C₄₂H₇₉NO₂
• 分子量: 630.095
• InChiKey: DVFYLRMZMPVFSD-KWXKLSQISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  14.8
• 重原子数：
  45
• 可旋转键数：
  36
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  21.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  亚麻醇 在 sodium hydride 、 三乙胺 作用下， 以 二氯甲烷 、 mineral oil 、 苯 为溶剂， 反应 11.0h， 生成 N,N-dimethyl-3,4-bis((9Z,12Z)-octadeca-9,12-dien-1-yloxy)butan-1-amine
  参考文献：
  名称：

  最大限度地提高 siRNA 脂质纳米颗粒在体内肝基因沉默中的效力

  摘要：

  特殊（脂质）递送：通过对脂质进行大量头基修饰，研究了可电离脂质 p K a在脂质纳米粒子体内递送 siRNA 中的作用。脂质P的的紧密相关ķ一个 值和鼠标FVII基因（FVII ED的沉默50）被发现，具有最佳p ķ一个范围的6.2-6.5（见图）。本研究中最有效的阳离子脂质的 ED 50水平在小鼠中约为 0.005 mg kg -1，在非人类灵长类动物中低于 0.03 mg kg -1。

  DOI：

  10.1002/anie.201203263

文献信息

• [EN] TRIALKYL CATIONIC LIPIDS AND METHODS OF USE THEREOF<br/>[FR] LIPIDES CATIONIQUES TRIALKYLÉS ET LEURS PROCÉDÉS D'UTILISATION
  申请人：PROTIVA BIOTHERAPEUTICS INC

  公开号：WO2013126803A1

  公开（公告）日：2013-08-29

  The present invention provides compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel, trialkyl, cationic lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of a specific target protein at relatively low doses.

  本发明提供了用于将治疗剂传递给细胞的组合物和方法。具体包括新颖的三烷基阳离子脂质和核酸-脂质颗粒，这些颗粒能够有效地封装核酸并将封装的核酸有效地传递给体内的细胞。本发明的组合物非常有效，因此可以在相对较低的剂量下有效地降低特定靶蛋白的表达。
• [EN] IMPROVED CATIONIC LIPIDS AND METHODS FOR THE DELIVERY OF THERAPEUTIC AGENTS<br/>[FR] LIPIDES CATIONIQUES ET PROCÉDÉS AMÉLIORÉS POUR L'ADMINISTRATION D'AGENTS THÉRAPEUTIQUES
  申请人：PROTIVA BIOTHERAPEUTICS INC

  公开号：WO2011000106A1

  公开（公告）日：2011-01-06

  The present invention provides compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel cationic lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of a specific target protein at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.

  本发明提供了用于将治疗剂传递到细胞的组合物和方法。具体包括新型阳离子脂质和核酸-脂质颗粒，它们能够有效地封装核酸并将封装的核酸有效地传递到体内的细胞中。本发明的组合物具有很高的效力，因此可以在相对较低的剂量下有效地降低特定靶蛋白的表达。此外，本发明的组合物和方法与先前已知的组合物和方法相比，毒性较低，提供更高的治疗指数。
• NON-LIPOSOMAL SYSTEMS FOR NUCLEIC ACID DELIVERY
  申请人：PROTIVA BIOTHERAPEUTICS, INC.

  公开号：US20160032320A1

  公开（公告）日：2016-02-04

  The present invention provides novel, stable lipid particles having a non-lamellar structure and comprising one or more active agents or therapeutic agents, methods of making such lipid particles, and methods of delivering and/or administering such lipid particles. More particularly, the present invention provides stable nucleic acid-lipid particles (SNALP) that have a non-lamellar structure and that comprise a nucleic acid (such as one or more interfering RNA), methods of making the SNALP, and methods of delivering and/or administering the SNALP.

  本发明提供了一种新颖的、稳定的脂质颗粒，具有非层状结构，包括一种或多种活性剂或治疗剂，以及制备这种脂质颗粒的方法，以及传递和/或给予这种脂质颗粒的方法。更具体地，本发明提供了稳定的核酸脂质颗粒（SNALP），其具有非层状结构，包括核酸（如一种或多种干扰RNA），制备SNALP的方法，以及传递和/或给予SNALP的方法。
• COMPOSITIONS AND METHODS FOR SILENCING APOLIPOPROTEIN B
  申请人：Heyes James

  公开号：US20130123339A1

  公开（公告）日：2013-05-16

  The present invention provides compositions and methods for the delivery of interfering RNAs such as siRNAs that silence APOB expression in cells such as liver cells. In particular, the nucleic acid-lipid particles provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells such as liver cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of APOB at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.

  本发明提供了一种用于传递干扰RNA（如siRNA）的组合物和方法，用于在细胞中（如肝细胞）沉默APOB表达。具体来说，核酸-脂质颗粒能够有效地封装核酸，并有效地将封装的核酸传递给体内的细胞，如肝细胞。本发明的组合物非常有效，因此可以在相对较低的剂量下有效地降低APOB的表达。此外，与先前已知的技术相比，本发明的组合物和方法毒性较低，并且提供了更大的治疗指数。
• COMPOSITIONS AND METHODS FOR DELIVERING MESSENGER RNA
  申请人：PROTIVA BIOTHERAPEUTICS, INC.

  公开号：US20160151284A1

  公开（公告）日：2016-06-02

  The present invention provides compositions comprising mRNA molecules encapsulated within lipid particles. The lipid particles comprise a cationic lipid, a non-cationic lipid, and an mRNA molecule that is encapsulated within the lipid particle. The compositions are useful, for example, to introduce the mRNA molecules into a human subject where they are translated to produce a polypeptide that functions to ameliorate one or more symptoms of a disease. The invention also provides cationic lipids that are useful for preparing the compositions of the invention.

  本发明提供了包含mRNA分子封装在脂质颗粒内的组合物。脂质颗粒包括一个阳离子脂质、一个非阳离子脂质和一个被封装在脂质颗粒内的mRNA分子。这些组合物可用于将mRNA分子引入人体受试者，从而产生一个多肽，其功能是改善一种或多种疾病症状。本发明还提供了用于制备上述组合物的阳离子脂质。