(S)-2-amino-6-(bis((1-(2-(bis(2-tert-butoxy-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino)hexanoic acid | 1228927-38-5

• 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: (S)-2-amino-6-(bis((1-(2-(bis(2-tert-butoxy-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino)hexanoic acid
• 英文别名: (2S)-2-amino-6-[bis[[1-[2-[bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]-2-oxoethyl]imidazol-2-yl]methyl]amino]hexanoic acid
• CAS: 1228927-38-5
• 化学式: C₄₂H₆₈N₈O₁₂
• 分子量: 877.048
• InChiKey: MUYAHVLEDSOTFX-LJAQVGFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  62
• 可旋转键数：
  30
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  248
• 氢给体数：
  2
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  (S)-2-amino-6-(bis((1-(2-(bis(2-tert-butoxy-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino)hexanoic acid 、 (S)-di-tert-butyl 2-(3-((S)-1-tert-butoxy-5-(2,5-dioxopyrrolidin-1-yloxy)-1,5-dioxopentan-2-yl)ureido)pentanedioate 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以84%的产率得到(2S,7S,11S)-2-(4-(bis((1-(2-(bis(2-tert-butoxy-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino)butyl)-7,11-bis(tert-butoxycarbonyl)-16,16-dimethyl-4,9,14-trioxo-15-oxa-3,8,10-triazaheptadecan-1-oic acid
  参考文献：
  名称：

  Synthesis and SAR of 99mTc/Re-labeled small molecule prostate specific membrane antigen inhibitors with novel polar chelates

  摘要：

  Prostate specific membrane antigen (PSMA) is recognized as an attractive molecular target for the development of radiopharmaceuticals to image and potentially treat metastatic prostate cancer. A series of novel Tc-99m/Re-tricarbonyl radiolabeled PSMA inhibitors were therefore synthesized by the attachment of glutamate-urea-lysine (Glu-urea-Lys) and glutamate-urea-glutamate (Glu-urea-Glu) pharmacophore to single amino acid chelate (SAAC) where the SAAC ligand was either bis(pyridin-2-ylmethyl)amino (DPA), bis((1-methyl-1H-imidazol-2-yl)methyl)amino (NMI), bis((1-(carboxymethyl)-1H-imidazol-2-yl)methyl)amino (CIM) or bis((1-(2-(bis(carboxymethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino (TIM). The in vitro binding affinity of the rhenium complexes was evaluated using PSMA-expressing human prostate cancer LNCaP cells. IC50 values ranged from 3.8 +/- 2 to > 2000 nM. A linker between the SAAC chelate and pharmacophore was required for high affinity binding. However, extending the length of the linker did not substantially improve binding. PSMA binding was also influenced by the nature of the SAAC chelate. One of the most potent compounds, 23b (IC50 = 4.8 +/- 2.7 nM), was radiolabeled with technetium tricarbonyl ({Tc-99m(CO)(3)}(+)) to afford the {Tc-99m(CO)(3)}(+) complex in excellent yield and high purity. This effort has led to the identification of a diverse series of promising high affinity {Tc-99m(CO)(3)}(+) radiolabeled PSMA inhibitors. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.09.014
• 作为产物：
  描述：

  tert-butyl 2,2′-(2-(2-formyl-1H-imidazol-1-yl)-acetylazanediyl)diacetate 在 哌啶 作用下， 以 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.5h， 生成 (S)-2-amino-6-(bis((1-(2-(bis(2-tert-butoxy-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino)hexanoic acid
  参考文献：
  名称：

  Bis(imidazolyl)compounds and radionuclide complexes

  摘要：

  公开号：

  EP2706057B1

文献信息

• TECHNETIUM- AND RHENIUM-BIS(HETEROARYL) COMPLEXES AND METHODS OF USE THEREOF
  申请人：BABICH John W.

  公开号：US20100183509A1

  公开（公告）日：2010-07-22

  Complexes of heterocyclic radionuclides are prepared based upon ligands having substituted pyridyl and imidazolyl groups. The ligands are bifunctional, having amino acid residues that may act as a linker to a bioactive molecule, and a tridentate chelator that may complex the radionuclide. The bioactive molecule may be a peptide or somatostatin.

  基于具有取代吡啶和咪唑基团的配体制备杂环放射性核素的复合物。配体是双功能的，具有可以作为生物活性分子连接器的氨基酸残基，以及可以络合放射性核素的三齿螯合剂。生物活性分子可以是肽或生长抑素。
• Technetium- and rhenium-bis(heteroaryl) complexes and methods of use thereof for inhibiting PSMA
  申请人：Molecular Insight Pharmaceuticals, Inc.

  公开号：US08211401B2

  公开（公告）日：2012-07-03

  A compound of Formula I, a pharmaceutically acceptable salt, or solvate thereof: complexes with metals such as rhenium, technetium, and others to provide a complex for imaging tissues or treating disease, particularly where the metal is radioactive. Such complexes are specific to PSMA protein and can therefore be used in imaging or treating cancer of the prostate and other tissue where the protein is expressed.

  公式I化合物，其药学上可接受的盐或溶剂化物：与铼、锝等金属形成络合物，用于成像组织或治疗疾病，特别是金属具有放射性的情况下。这样的络合物是特异性的PSMA蛋白质，因此可以用于成像或治疗前列腺癌和其他组织中表达该蛋白质的癌症。
• TECHNETIUM- AND RHENIUM-BIS(HETEROARYL) COMPLEXES AND METHODS OF USE THEREOF FOR INHIBITING PSMA
  申请人：Babich John W.

  公开号：US20100178246A1

  公开（公告）日：2010-07-15

  A compound of Formula I, a pharmaceutically acceptable salt, or solvate thereof: complexes with metals such as rhenium, technetium, and others to provide a complex for imaging tissues or treating disease, particularly where the metal is radioactive. Such complexes are specific to PSMA protein and can therefore be used in imaging or treating cancer of the prostate and other tissue where the protein is expressed.

  公式I的化合物，其药学上可接受的盐或溶剂化物：与金属如铼、锝等形成络合物，以提供成像组织或治疗疾病的复合物，特别是当金属具有放射性时。这些复合物针对PSMA蛋白质具有特异性，因此可以用于成像或治疗前列腺癌和其他表达该蛋白质的组织。
• Technetium- and rhenium-bis(heteroaryl) complexes and methods of use thereof
  申请人：Babich John W.

  公开号：US08562945B2

  公开（公告）日：2013-10-22

  Complexes of heterocyclic radionuclides are prepared based upon ligands having substituted pyridyl and imidazolyl groups. The ligands are bifunctional, having amino acid residues that may act as a linker to a bioactive molecule, and a tridentate chelator that may complex the radionuclide. The bioactive molecule may be a peptide or somatostatin.

  以带有取代的吡啶基和咪唑基的配体为基础制备杂环放射性核素的配合物。该配体是双功能的，具有可以作为生物活性分子连接器的氨基酸残基和可以络合放射性核素的三齿螯合剂。生物活性分子可以是肽或生长抑素。
• Technetium—and rhenium-bis(heteroaryl) complexes and methods of use thereof
  申请人：Molecular Insight Pharmaceuticals, Inc.

  公开号：US08962799B2

  公开（公告）日：2015-02-24

  A method of imaging a region in a subject includes administering to the subject a complex of a metal chelated to a compound, and obtaining an image of the region in the subject.

  一种成像主体中的区域的方法包括向主体注射金属配合物复合物，并获取该主体区域的图像。