4,4'-[[[[3-(dimethylamino)propyl]thio]carbonyl]imino]bis-butanoic acid bis-(8-pentadecanoyl) ester | 2230647-37-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物
• 英文名称: 4,4'-[[[[3-(dimethylamino)propyl]thio]carbonyl]imino]bis-butanoic acid bis-(8-pentadecanoyl) ester
• 英文别名: Di(pentadecan-8-yl) 4,4'-((((3-(dimethylamino)propyl)thio)carbonyl)azanediyl)dibutyrate；pentadecan-8-yl 4-[3-(dimethylamino)propylsulfanylcarbonyl-(4-oxo-4-pentadecan-8-yloxybutyl)amino]butanoate
• CAS: 2230647-37-5
• 化学式: C₄₄H₈₆N₂O₅S
• 分子量: 755.243
• InChiKey: HAWZMEVIHSUELL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  15.2
• 重原子数：
  52
• 可旋转键数：
  41
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  101
• 氢给体数：
  0
• 氢受体数：
  7

安全信息

• 危险性防范说明：
  P501,P270,P264,P280,P302+P352,P337+P313,P305+P351+P338,P362+P364,P332+P313,P301+P312+P330
• 危险性描述：
  H302,H315,H319

反应信息

• 作为产物：
  描述：

  dimethyl 4,4'-(benzylazanediyl)dibutyrate 在 palladium 10% on activated carbon 、 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 61.41h， 生成 4,4'-[[[[3-(dimethylamino)propyl]thio]carbonyl]imino]bis-butanoic acid bis-(8-pentadecanoyl) 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

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。
• ASIALOGLYCOPROTEIN RECEPTOR MEDIATED DELIVERY OF THERAPEUTICALLY ACTIVE CONJUGATES
  申请人：Arcturus Therapeutics, Inc.

  公开号：US20210060168A1

  公开（公告）日：2021-03-04

  ASGP-R binding molecular conjugates are provided. The conjugates are useful to deliver therapeutically effective amounts of biologically active molecules to target cells and tissues of a subject. Compositions are also provided comprising the molecular conjugates.

  提供ASGP-R结合分子共轭物。这些共轭物可用于将治疗有效量的生物活性分子传递给受试者的靶细胞和组织。还提供包含这些分子共轭物的组合物。
• Ionizable cationic lipid for RNA delivery
  申请人：Arcturus Therapeutics, Inc.

  公开号：US10961188B2

  公开（公告）日：2021-03-30

  Disclosed herein is a compound of Formula I, wherein 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 or solvate thereof.

  本文公开了一种式 I 的化合物，其中 R1 是由 10 至 31 个碳组成的支链烷基；R2 是由 2 至 20 个碳组成的直链烷基、烯基或炔基，或由 10 至 31 个碳组成的支链烷基；L1 和 L2 相同或不同，各自是由 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是S或O；R3是由1至6个碳组成的直链或支链亚烷基；R4和R5相同或不同，各自是氢或由1至6个碳组成的直链或支链烷基；或其药学上可接受的盐或溶液。
• Therapeutics for glycogen storage disease type III
  申请人：Ultragenyx Pharmaceutical Inc.

  公开号：US11377643B2

  公开（公告）日：2022-07-05

  This invention provides a range of translatable polynucleotide and oligomer molecules for expressing a human amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase (AGL), or a fragment thereof having AGL activity. The polynucleotide and oligomer molecules are expressible to provide the human AGL or a fragment thereof having AGL activity. The molecules can be used as active agents to express an active polypeptide or protein in cells or subjects. The agents can be used in methods for ameliorating, preventing, delaying onset, or treating a disease or condition associated with reduced activity of amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase (AGL) in a subject.

  本发明提供了一系列可翻译的多核苷酸和寡聚体分子，用于表达人淀粉-α-1，6-葡萄糖苷酶、4-α-葡聚糖转移酶（AGL）或其具有 AGL 活性的片段。多核苷酸和寡聚物分子可表达出具有 AGL 活性的人 AGL 或其片段。这些分子可用作活性制剂，在细胞或人体中表达活性多肽或蛋白质。这些制剂可用于改善、预防、推迟发病或治疗与受试者体内淀粉-α-1，6-葡萄糖苷酶、4-α-葡聚糖转移酶（AGL）活性降低有关的疾病或病症的方法。
• Development of a Safe and Scalable Process for the Production of a High-Purity Thiocarbamate-Based Ionizable Lipid as an Excipient in mRNA-Encapsulating Lipid Nanoparticles
  作者：Kumar Rajappan、Steven P. Tanis、Scott Roberts、Priya Karmali、Padmanabh Chivukula、Jin Zhuang、Mingxing Xin、Manman Zheng、Ian Edmonds

  DOI：10.1021/acs.oprd.1c00076

  日期：2021.6.18