4,4'-[[(1,1-dimethylethoxy)carbonyl]imino]bisbutanoic acid | 1204700-92-4

• 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: 4,4'-[[(1,1-dimethylethoxy)carbonyl]imino]bisbutanoic acid
• 英文别名: 4,4'-((tert-butoxycarbonyl)azanediyl)dibutyric acid；4-[tert-butoxycarbonyl-carbonylpropyl-amino]-butanoic acid；4-[3-carboxypropyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]butanoic acid
• CAS: 1204700-92-4
• 化学式: C₁₃H₂₃NO₆
• 分子量: 289.329
• InChiKey: HDBYWYDMUACFKH-UHFFFAOYSA-N

物化性质

• 沸点：
  480.1±38.0 °C(Predicted)
• 密度：
  1.189±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  20
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4,4'-[[(1,1-dimethylethoxy)carbonyl]imino]bisbutanoic acid 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 31.16h， 生成 4-((((2-(dimethylamino)ethyl)thio)carbonyl)(4-oxo-4-(heptdecan-9-yloxy)butyl)amino)butanoate (Z)-non-2-en-1-yl ester
  参考文献：
  名称：

  Property-Driven Design and Development of Lipids for Efficient Delivery of siRNA

  摘要：

  Ionizable cationic lipids are critical components involved in nanoparticle formulations, which are utilized in delivery platforms for RNA therapeutics. While general criteria regarding lipophilicity and measured pK(a) in formulation are understood to have impacts on utility in vivo, greater granularity with respect to the impacts of the structure on calculated and measured physicochemical parameters and the subsequent performance of those ionizable cationic lipids in in vivo studies would be beneficial. Herein, we describe structural alterations made within a lipid class exemplified by 4, which allow us to tune calculated and measured physicochemical parameters for improved performance, resulting in substantial improvements versus the state of the art at the outset of these studies, resulting in good in vivo activity within a range of measured basicity (pK(a) = 6.0-6.6) and lipophilicity (cLogD = 10-14).

  DOI：

  10.1021/acs.jmedchem.0c01407
• 作为产物：
  描述：

  dimethyl 4,4'-(benzylazanediyl)dibutyrate 在 palladium 10% on activated carbon 、 氢气 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 19.0h， 生成 4,4'-[[(1,1-dimethylethoxy)carbonyl]imino]bisbutanoic acid
  参考文献：
  名称：

  Property-Driven Design and Development of Lipids for Efficient Delivery of siRNA

  摘要：

  Ionizable cationic lipids are critical components involved in nanoparticle formulations, which are utilized in delivery platforms for RNA therapeutics. While general criteria regarding lipophilicity and measured pK(a) in formulation are understood to have impacts on utility in vivo, greater granularity with respect to the impacts of the structure on calculated and measured physicochemical parameters and the subsequent performance of those ionizable cationic lipids in in vivo studies would be beneficial. Herein, we describe structural alterations made within a lipid class exemplified by 4, which allow us to tune calculated and measured physicochemical parameters for improved performance, resulting in substantial improvements versus the state of the art at the outset of these studies, resulting in good in vivo activity within a range of measured basicity (pK(a) = 6.0-6.6) and lipophilicity (cLogD = 10-14).

  DOI：

  10.1021/acs.jmedchem.0c01407

文献信息

• IONIZABLE CATIONIC LIPID FOR RNA DELIVERY
  申请人：Arcturus Therapeutics, Inc.

  公开号：US20180170866A1

  公开（公告）日：2018-06-21

  What is described is a compound of formula I consisting of a compound in which R 1 is a branched chain alkyl consisting of 10 to 31 carbons; R 2 is a linear alkyl, alkenyl, or alkynyl consisting of 2 to 20 carbons, or a branched chain alkyl consisting of 10 to 31 carbons; L 1 and L 2 are the same or different, each a linear alkane of 1 to 20 carbons or a linear alkene of 2 to 20 carbons; X 1 is S or O; R 3 is a linear or branched alkylene consisting of 1 to 6 carbons; and R 4 and R 5 are the same or different, each a hydrogen or a linear or branched alkyl consisting of 1 to 6 carbons; or a pharmaceutically acceptable salt thereof.

  描述的是一种化合物，其化学式为I，包括以下成分： R1为由10至31个碳组成的支链烷基； R2为由2至20个碳组成的直链烷基、烯烃或炔烃，或者由10至31个碳组成的支链烷基； L1和L2相同或不同，每个为由1至20个碳组成的直链烷烃或由2至20个碳组成的直链烯烃； X1为S或O； R3为由1至6个碳组成的直链或支链烷基；以及 R4和R5相同或不同，每个为氢或由1至6个碳组成的直链或支链烷基；或其药用可接受盐。
• Syntheses of Glycoclusters Containing a Phosphocholine Residue Related to a Glycosphingolipid from the Earthworm Pheretima hilgendorfi
  作者：Noriyasu Hada、Yukihiko Shida、Natsuko Negishi、Frank Schweizer、Tadahiro Takeda

  DOI：10.1248/cpb.57.1081

  日期：——

  Three types of glycoclusters related to an amphoteric glycosphingolipid found in the earthworm Pheretima hilgendorfi were synthesized. The glycoclusters were prepared from a common precursor and a simple approach for the rational design of a glycocluster was developed.

  从蚯蚓Pheretima hilgendorfi中发现的一种两性糖神经酰胺相关联的三种类型的糖簇被成功合成。这些糖簇是从一个共同的先体制备而成，并且开发出了一种简便的方法来对糖簇进行合理设计。
• [EN] IONIZABLE CATIONIC LIPIDS FOR RNA DELIVERY<br/>[FR] LIPIDES CATIONIQUES IONISABLES POUR L'ACHEMINEMENT D'ARN
  申请人：ARCTURUS THERAPEUTICS INC

  公开号：WO2023086514A1

  公开（公告）日：2023-05-19

  The present disclosure describes compounds of Formula (I) and pharmaceutically acceptable salts thereof.

  本公开说明书描述了公式（I）的化合物及其药学上可接受的盐。
• [EN] IONIZABLE CATIONIC LIPID FOR RNA DELIVERY<br/>[FR] LIPIDE CATIONIQUE IONISABLE POUR L'ADMINISTRATION D'ARN
  申请人：PAYNE JOSEPH E

  公开号：WO2018119163A1

  公开（公告）日：2018-06-28

  What is described is a compound of formula (I) consisting of a compound in which R1 is a branched chain alkyl consisting of 10 to 31 carbons; R2 is a linear alkyl, alkenyl, or alkynyl consisting of 2 to 20 carbons, or a branched chain alkyl consisting of 10 to 31 carbons; L1 and L2 are the same or different, each a linear alkane of 1 to 20 carbons or a linear alkene of 2 to 20 carbons; X1 is S or O; R3 is a linear or branched alkylene consisting of 1 to 6 carbons; and R4 and R5 are the same or different, each a hydrogen or a linear or branched alkyl consisting of 1 to 6 carbons; or a pharmaceutically acceptable salt thereof.
• Property-Driven Design and Development of Lipids for Efficient Delivery of siRNA
  作者：Kumar Rajappan、Steven P. Tanis、Rajesh Mukthavaram、Scott Roberts、Michelle Nguyen、Kiyoshi Tachikawa、Amit Sagi、Marciano Sablad、Pattraranee Limphong、Angel Leu、Hailong Yu、Padmanabh Chivukula、Joseph E. Payne、Priya Karmali

  DOI：10.1021/acs.jmedchem.0c01407

  日期：2020.11.12

  Ionizable cationic lipids are critical components involved in nanoparticle formulations, which are utilized in delivery platforms for RNA therapeutics. While general criteria regarding lipophilicity and measured pK(a) in formulation are understood to have impacts on utility in vivo, greater granularity with respect to the impacts of the structure on calculated and measured physicochemical parameters and the subsequent performance of those ionizable cationic lipids in in vivo studies would be beneficial. Herein, we describe structural alterations made within a lipid class exemplified by 4, which allow us to tune calculated and measured physicochemical parameters for improved performance, resulting in substantial improvements versus the state of the art at the outset of these studies, resulting in good in vivo activity within a range of measured basicity (pK(a) = 6.0-6.6) and lipophilicity (cLogD = 10-14).