N-(trifluoroacetaminohexanoyl)aspartic acid | 1279699-71-6

• 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: N-(trifluoroacetaminohexanoyl)aspartic acid
• 英文别名: N-(6-trifluroacetamidohexanoyl)-L-aspartic acid；Nα-(trifluoroacetaminohexanoyl)aspartic acid；(S)-2-(6-(2,2,2-Trifluoroacetamido)hexanamido)succinicacid；(2S)-2-[6-[(2,2,2-trifluoroacetyl)amino]hexanoylamino]butanedioic acid
• CAS: 1279699-71-6
• 化学式: C₁₂H₁₇F₃N₂O₆
• 分子量: 342.272
• InChiKey: DXYMKGOWWDHHLL-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  23
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  133
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-(trifluoroacetaminohexanoyl)aspartic acid 、 在 2-肟氰乙酸乙酯 、 N,N'-二异丙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以77%的产率得到
  参考文献：
  名称：

  Development of single vial kits for preparation of⁶⁸Ga-labelled hexavalent lactoside for PET imaging of asialoglycoprotein receptor

  摘要：

  本研究的目的是制定和评估 NOTA 六价乳糖苷 (NOTA-HL) 冻干试剂盒，用于制备用于脱唾液酸糖蛋白受体 (ASGPR) PET 成像的 68Ga 标记糖配体。 68GaCl3 是从商用 68Ge/68Ga 发生器获得的。配制单瓶 HL 试剂盒。进行了 68Ga 放射性标记的优化、NOTA-HL 试剂盒的各种评估以及 68Ga-HL 的体外稳定性研究。对注射 68Ga-NOTA-HL 的正常小鼠进行 PET/CT 成像。 NOTA-HL试剂盒配制成功。通过 68Ga 放射性标记获得了高放射化学产率 (>95%)。 NOTA-HL 试剂盒稳定至少 12 个月，68Ga-NOTA-HL 表现出良好的体外稳定性。对正常小鼠的 PET 研究显示肝脏中活性的高特异性积累。 NOTA-HL 试剂盒专为快速 68Ga 标记而开发。 68Ga-NOTA-HL 在肝脏中表现出高特异性摄取。即用型 NOTA-HL 套件与 68Ge/68Ga 发生器相结合，将为 ASGPR 的 PET 成像提供有效的方法。

  DOI：

  10.1002/jlcr.3673
• 作为产物：
  描述：

  N-(6-trifluroacetamidohexanoyl)-L-aspartic acid dibenzyl ester 在 palladium 10% on activated carbon 氢气 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 生成 N-(trifluoroacetaminohexanoyl)aspartic acid
  参考文献：
  名称：

  NOVEL LIVER-TARGETING AGENTS AND THEIR SYNTHESIS

  摘要：

  该发明提供了新型的肝靶向药物及其合成方法。一种肝靶向药物，以赖氨酸为骨架，具有氨基三乙酸结构，通过与糖苷基团形成多价性，与半乳糖胺链或乳糖链结合。具体来说，仅涉及一种氨基酸L-赖氨酸，以提供三价性。Nε-苄氧羰基-Nα-二羧甲基-L-赖氨酸中的所有羧基可以在一步中与三个ahGalNAc或ahLac的糖苷结合。该发明还提供了一种六乳糖苷。具体来说，TFA-AHA-Asp被用于将2摩尔的NTA(ahLac)3结合。该发明还提供了一种在NTA和DTPA之间添加间隔物的方法。扩展的肝细胞特异性糖基配体的111In标记产率高于非扩展的配体。

  公开号：

  US20110077386A1

文献信息

• NOVEL LIVER-TARGETING AGENTS AND THEIR SYNTHESIS
  申请人：LEE REIKO TAKASAKA

  公开号：US20110077386A1

  公开（公告）日：2011-03-31

  This invention provides novel liver targeting agents and their synthetic methods. A liver targeting agent, with a lysine based nitrilo triacetic acid structure as backbone which acquires multivalency with saccharide groups, to bind with a galactosamine chain or lactose chain is disclosed. In particular, only one amino acid L-lysine is involved to provide trivalency. All carboxyl groups in N ε -benzyloxycarbonyl-N α -dicarboxymethyl-L-lysine can be conjugated with three glycosides of ahGalNAc or ahLac in one step. This invention also provides a hexa-lactoside. In particular, the TFA-AHA-Asp was used to conjugate 2 moles of NTA(ahLac) 3 . This invention also provides a method for adding a spacer between NTA and DTPA. The extended hepatocyte-specific glyco-ligand has higher 111 In-radiolabelling yield than those non-extended.

  该发明提供了新型的肝靶向药物及其合成方法。一种肝靶向药物，以赖氨酸为骨架，具有氨基三乙酸结构，通过与糖苷基团形成多价性，与半乳糖胺链或乳糖链结合。具体来说，仅涉及一种氨基酸L-赖氨酸，以提供三价性。Nε-苄氧羰基-Nα-二羧甲基-L-赖氨酸中的所有羧基可以在一步中与三个ahGalNAc或ahLac的糖苷结合。该发明还提供了一种六乳糖苷。具体来说，TFA-AHA-Asp被用于将2摩尔的NTA(ahLac)3结合。该发明还提供了一种在NTA和DTPA之间添加间隔物的方法。扩展的肝细胞特异性糖基配体的111In标记产率高于非扩展的配体。
• NOVEL GALL BLADDER IMAGING AGENT AND ITS PREPARATION METHOD
  申请人：INSTITUTE OF NUCLEAR ENERGY RESEARCH ATOMIC ENERGY COUNCIL, EXECUTIVE YUAN

  公开号：US20140186262A1

  公开（公告）日：2014-07-03

  A novel gall bladder image agent which includes a radio-labelled MAG3-tri-galactosamine, and its preparation method, which includes reacting mercaptoacetyltriglycine (MAG3)-tri-galactosamine, SnF2 and Tc-99m in the presence of a phosphate buffer solution (at pH of from 10.0˜12.0) to obtain Tc-99m-MAG3-tri-galactosamine, when the MAG3-tri-galactosamine is MAG3-DCM-Lys(Gah-GalNAc)3 (where DCM represents a dicarboxymethyl group, and Gah represents a glycine-aminohexyl group), it obtains a labelling yield of at least 90%, and its specific radioactivity is at least 7.0×109 Bq/mg.

  一种新型的胆囊成像剂，包括放射性标记的MAG3-三半乳糖胺，并且其制备方法包括在磷酸盐缓冲溶液（pH值在10.0~12.0之间）中反应巯基乙酰三甘氨酸（MAG3）-三半乳糖胺、SnF2和Tc-99m，以获得Tc-99m-MAG3-三半乳糖胺，当MAG3-三半乳糖胺是MAG3-DCM-Lys（Gah-GalNAc）3（其中DCM代表二羧甲基基团，Gah代表甘氨酰己基基团）时，获得至少90％的标记收率，其特异性放射性至少为7.0×109 Bq/mg。
• US9226982B2
  申请人：——

  公开号：US9226982B2

  公开（公告）日：2016-01-05
• New and more efficient multivalent glyco-ligands for asialoglycoprotein receptor of mammalian hepatocytes
  作者：Reiko T. Lee、Mei-Hui Wang、Wuu-Jyh Lin、Yuan C. Lee

  DOI：10.1016/j.bmc.2011.03.027

  日期：2011.4

  New multi-valent, carbohydrate ligands that contain terminal N-acetylgalactosamine (GalNAc) or lactose (Lac) were prepared using a nitrilotriacetic acid (NTA) derivative of L-lysine as scaffold. Tri-valent structures were prepared by attaching an x-amino glycoside of GalNAc or Lac to each of the three carboxyl groups of N-epsilon-protected N-alpha-dicarboxymethyl-L-lysine. In addition, a hexa-valent lactoside was synthesized by attaching N-epsilon-deprotected trivalent lactoside to each of the carboxyl group of N-alpha-(trifluoroacetamido) hexanoyl L-aspartic acid. Tri-valent GalNAc glycosides and the hexa-valent lactoside had high affinity (dissociation constants approaching nM) for rat hepatocytes. The hexa-valent lactoside, after de-Ne-protection, was modified with a chelator, diethylenetriaminepentaacetic acid (DTPA), through which a fluorescent or radioactive tag, such as europium or indium, can be firmly attached. Intravenous infusion of (111)Indium-tagged hexa-valent lactoside to rats and mice resulted in nearly exclusive accumulation of radioactivity in the liver.(C) 2011 Elsevier Ltd. All rights reserved.
• Development of single vial kits for preparation of⁶⁸Ga-labelled hexavalent lactoside for PET imaging of asialoglycoprotein receptor
  作者：Hung-Man Yu、Chen-Hsin Chan、Jyun-Hong Chen、Chuan-Yi Chien、Ping-Yen Wang、Wei-Cheng Juan、Chun-Hung Yang、Hao-Ting Hsia、Mei-Hui Wang、Wuu-Jyh Lin

  DOI：10.1002/jlcr.3673

  日期：2018.10

  The aim of this study was to formulate and evaluate the freeze-dried kit of NOTA-hexavalent lactoside (NOTA-HL) for the preparation of 68Ga-labeled glycoligand for PET imaging of the asialoglycoprotein receptor (ASGPR). 68GaCl3 was obtained from a commercial 68Ge/68Ga generator. Single-vial kits of HL were formulated. Optimization of radiolabeling with 68Ga, various evaluations of NOTA-HL kits, and in vitro stability study of 68Ga-HL were carried out. PET/CT imaging of normal mice injected with 68Ga-NOTA-HL was performed. NOTA-HL kit was successfully formulated. High radiochemical yields (>95%) were obtained by 68Ga radiolabeling. The NOTA-HL kits were stable for at least 12 months, and 68Ga-NOTA-HL exhibited good in vitro stability. PET studies in normal mice revealed high specific accumulation of activity in the liver. The NOTA-HL kit was developed for fast 68Ga labeling. 68Ga-NOTA-HL showed high specific uptake in liver. The availability of ready-to-use NOTA-HL kits combined with 68Ge/68Ga generators would provide an efficient approach for PET imaging of ASGPR.

  本研究的目的是制定和评估 NOTA 六价乳糖苷 (NOTA-HL) 冻干试剂盒，用于制备用于脱唾液酸糖蛋白受体 (ASGPR) PET 成像的 68Ga 标记糖配体。 68GaCl3 是从商用 68Ge/68Ga 发生器获得的。配制单瓶 HL 试剂盒。进行了 68Ga 放射性标记的优化、NOTA-HL 试剂盒的各种评估以及 68Ga-HL 的体外稳定性研究。对注射 68Ga-NOTA-HL 的正常小鼠进行 PET/CT 成像。 NOTA-HL试剂盒配制成功。通过 68Ga 放射性标记获得了高放射化学产率 (>95%)。 NOTA-HL 试剂盒稳定至少 12 个月，68Ga-NOTA-HL 表现出良好的体外稳定性。对正常小鼠的 PET 研究显示肝脏中活性的高特异性积累。 NOTA-HL 试剂盒专为快速 68Ga 标记而开发。 68Ga-NOTA-HL 在肝脏中表现出高特异性摄取。即用型 NOTA-HL 套件与 68Ge/68Ga 发生器相结合，将为 ASGPR 的 PET 成像提供有效的方法。