ethyl 6-(dimethylamino)hexanoate | 2508-32-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: ethyl 6-(dimethylamino)hexanoate
• CAS: 2508-32-9
• 化学式: C₁₀H₂₁NO₂
• 分子量: 187.282
• InChiKey: MLRLKCCSQCCSED-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  13
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 6-(dimethylamino)hexanoate 在 sodium hydroxide 、 盐酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 2.0h， 生成 6-(dimethylamino)hexanoic acid hydrochloride
  参考文献：
  名称：

  COMPOSITIONS AND METHODS FOR SILENCING APOLIPOPROTEIN B

  摘要：

  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。

  公开号：

  US20130123339A1
• 作为产物：
  描述：

  6-羟基己酸乙酯 在 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 24.0h， 生成 ethyl 6-(dimethylamino)hexanoate
  参考文献：
  名称：

  NON-LIPOSOMAL SYSTEMS FOR NUCLEIC ACID DELIVERY

  摘要：

  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。

  公开号：

  US20160032320A1

文献信息

• 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。
• Esters and amides of hexanoic acid substituted with tertiary amino group in terminal position and their activity as transdermal permeation enhancers
  作者：Oldřich Farsa、Pavel Dolezal、Alexandr Hrabálek

  DOI：10.2298/jsc090527034f

  日期：——

  Series of alkyl esters of 6-diethylamino-, 6-(pyrrolidin-1-yl)-, 6- (piperidin-1-yl) and 6-(morpholin-1-yl)hexanoic acids and alkylamides of 6-dimethylamino-, 6-(piperidin-1-yl) and 6-(morpholin-1-yl)hexanoic acids, containing 8-12 carbon atoms in the alkyl chain, were prepared by methods of classical organic synthesis. The appropriate secondary amine was alkylated with ethyl-6-bromohexanoate to give ester of ?-substituted hexanoic acid, except of ethyl-6-dimethylaminohexanoate (1), which was prepared by Eschweiler-Clarke methylation of 6-aminohexanoic acid followed by direct esterification with ethanol. The resulted esters of ?-substituted hexanoic acids underwent direct transesterification with long chain alkanols to yield the desired amino esters, or they were treated with long-chain alkylamines to prepare secondary amides of the appropriate heterocyclic hexanoic acids. These products were in vitro tested on their activity as transdermal permeation enhancers on the strips of the excised human skin with theophylline as the model permeant. The activity was evaluated using parameter enhancement ratio (ER), defined as the ratio between the overall amount of the permeant passing through the skin with the tested enhancer and that without tested substance. Decyl 6-(pyrrolidin- 1-yl)hexanoate (16) with ER = 30 showed the highest activity. The enhancing effects of the esters were generally better than those of the amides.

  采用经典有机合成方法制备了烷基链中含有 8-12 个碳原子的 6-二乙氨基-、6-（吡咯烷-1-基）-、6-（哌啶-1-基）和 6-（吗啉-1-基）己酸的烷基酯和 6-二甲氨基-、6-（哌啶-1-基）和 6-（吗啉-1-基）己酸的烷基酰胺系列。适当的仲胺与 6-溴己酸乙酯发生烷基化反应，得到被取代的己酸酯，但 6-二甲氨基己酸乙酯（1）除外，它是通过 6-氨基己酸的埃施韦勒-克拉克甲基化反应，然后用乙醇直接酯化制备的。生成的?-取代己酸酯直接与长链烷醇进行酯交换反应，生成所需的氨基酯，或者用长链烷胺处理，制备适当杂环己酸的仲酰胺。以茶碱为模型渗透剂，对这些产品作为透皮渗透促进剂在切除的人体皮肤条上的活性进行了体外测试。其活性是通过参数增强比（ER）来评估的，参数增强比的定义是渗透剂通过皮肤的总量与未加入受测物质的渗透剂通过皮肤的总量之比。ER=30的6-（吡咯烷-1-基）己酸癸酯（16）显示出最高的活性。酯类的增强效果普遍优于酰胺类。
• A DNA-binding Gd chelate for the detection of cell death by MRI
  作者：Elisabeth Garanger、Scott A. Hilderbrand、Joseph T. Blois、David E. Sosnovik、Ralph Weissleder、Lee Josephson

  DOI：10.1039/b907375b

  日期：——

  GadoTO, a MR contrast agent for the detection of cell death, consists of a nucleic acid-binding fluorophore attached to a gadolinium chelate.

  GadoTO 是一种用于检测细胞死亡的磁共振造影剂，由一个核酸结合荧光团和一个钆螯合物组成。
• VITAL FLUOROCHROME CONJUGATES AND METHODS OF USE
  申请人：Josephson Lee

  公开号：US20120121509A1

  公开（公告）日：2012-05-17

  The present invention provides compositions and methods based on vital fluorochrome conjugates that are useful for imaging dying and dead cells.

  本发明提供了基于活性荧光染料结合物的组合物和方法，用于成像死亡和死亡细胞。
• Compositions and methods for silencing apolipoprotein B
  申请人：Heyes James

  公开号：US08865675B2

  公开（公告）日：2014-10-21

  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.

  本发明提供了一种组合物和方法，用于递送干扰RNA（如siRNA）以在细胞中（如肝细胞）沉默APOB表达。特别地，核酸脂质颗粒提供了高效的核酸封装和有效的封装核酸递送到体内的细胞（如肝细胞）。本发明的组合物具有高度的效力，因此可以在相对较低的剂量下有效地抑制APOB。此外，本发明的组合物和方法比先前已知的组合物和方法更少毒性，提供更大的治疗指数。