(((S)-1-carboxy-5-(8-((2,5-dioxopyrrolidin-1-yl)oxy)-8 oxooctanamido)pentyl)carbamoyl)-Lglutamicacid | 1159849-86-1

• 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)-1-carboxy-5-(8-((2,5-dioxopyrrolidin-1-yl)oxy)-8 oxooctanamido)pentyl)carbamoyl)-Lglutamicacid
• 英文别名: DCL-DSS；2-(3-{1-carboxy-5-[7-(2,5-dioxo-pyrrolidin-1-yloxycarbonyl)-heptanoylamino]-pentyl}-ureido)-pentanedioic acid；(2S)-2-[[(1S)-1-carboxy-5-[[8-(2,5-dioxopyrrolidin-1-yl)oxy-8-oxooctanoyl]amino]pentyl]carbamoylamino]pentanedioic acid
• CAS: 1159849-86-1
• 化学式: C₂₄H₃₆N₄O₁₂
• 分子量: 572.569
• InChiKey: XOPZZFMVMBMJQJ-HOTGVXAUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  40
• 可旋转键数：
  21
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  246
• 氢给体数：
  6
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  (((S)-1-carboxy-5-(8-((2,5-dioxopyrrolidin-1-yl)oxy)-8 oxooctanamido)pentyl)carbamoyl)-Lglutamicacid 在 哌啶 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 C₃₀H₅₁N₇O₁₃
  参考文献：
  名称：

  Effect of Chelators on the Pharmacokinetics of ^99mTc-Labeled Imaging Agents for the Prostate-Specific Membrane Antigen (PSMA)

  摘要：

  Technetium-99m, the most commonly used radionuclide in nuclear medicine, can be attached to biologically important molecules through a variety of chelating agents, the choice of which depends upon the imaging application. The prostate-specific membrane antigen (PSMA) is increasingly recognized as an important target for imaging and therapy of prostate cancer (PCa). Three different Tc-99m-labeling methods were employed to investigate the effect of the chelator on the biodistribution and PCa tumor uptake profiles of 12 new urea-based PSMA-targeted radiotracers. This series includes hydrophilic ligands for radiolabeling with the [Tc-99m(CO)(3)](+) core (L8-L10), traditional NxSy-based chelating agents with varying charge and polarity for the Tc-99m-oxo core (L11-L18), and a Tc-99m-organohydrazine-labeled radioligand (L19). Tc-99m(I)-Tricarbonyl-labeled [Tc-99m]L8 produced the highest PSMA+ PC3 PIP to PSMA- PC3 flu tumor ratios and demonstrated the lowest retention in normal tissues including kidney after 2 h. These results suggest that choice of chelator is an important pharmacokinetic consideration in the development of Tc-99m-labeled radiopharmaceuticals targeting PSMA.

  DOI：

  10.1021/jm400823w
• 作为产物：
  描述：

  双琥珀酰亚胺辛二酸酯 在 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.33h， 生成 (((S)-1-carboxy-5-(8-((2,5-dioxopyrrolidin-1-yl)oxy)-8 oxooctanamido)pentyl)carbamoyl)-Lglutamicacid
  参考文献：
  名称：

  具有前列腺特异性膜抗原双模态抑制剂的前列腺癌实验模型的序贯 SPECT 和光学成像

  摘要：

  两种技术的一种试剂：化合物 [ 111 In] 1通过靶向前列腺特异性膜抗原，为前列腺癌的连续放射性核素和光学成像提供了平台。由于同一受试者在注射一次药物后可以进行双重成像，因此这些发现支持快速临床转化。

  DOI：

  10.1002/anie.201102872

文献信息

• [EN] METAL/RADIOMETAL-LABELED PSMA INHIBITORS FOR PSMA-TARGETED IMAGING AND RADIOTHERAPY<br/>[FR] INHIBITEURS DU PSMA MARQUÉS PAR UN MÉTAL/RADIOMÉTAL POUR IMAGERIE ET RADIOTHÉRAPIE CIBLÉES VERS LE PSMA
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2015171792A1

  公开（公告）日：2015-11-12

  Low-molecular weight gadolinium (Gd)-based MR contrast agents for PSMA- specific Ti-weighted MR imaging are disclosed. The (Gd)-based MR contrast agents exhibit high binding affinity for PSMA and exhibit specific Ti contrast enhancement at PSMA+ cells. The PSMA-targeted Gd-based MR contrast agents can be used for PSMA- targeted imaging in vivo. 86Y-labeled PSMA-binding ureas also are provided, wherein the PSMA-binding ureas also are suitable for use with other radiotherapeutics.

  低分子量钆（Gd）基MR对比剂用于PSMA特异性Ti加权MR成像。这些基于Gd的MR对比剂具有高结合亲和力，可在PSMA+细胞中显示特定的Ti对比增强。PSMA靶向的基于Gd的MR对比剂可用于体内PSMA靶向成像。还提供了86Y标记的PSMA结合脲，其中这些PSMA结合脲也适用于与其他放射治疗药物一起使用。
• Modular Synthesis of DOTA‐Metal‐Based PSMA‐Targeted Imaging Agents for MRI and PET of Prostate Cancer
  作者：Hans F. Schmitthenner、Damien E. Dobson、Kelsea G. Jones、Nnamdi Akporji、Dana Q. M. Soika、Kent L. Nastiuk、Joseph P. Hornak

  DOI：10.1002/chem.201903390

  日期：2019.11.4

  practical, convergent synthesis of prostate-specific membrane antigen (PSMA) targeted imaging agents for MRI, PET, and SPECT of prostate cancer has been developed. In this approach, metals chelated to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) were placed on the side chains of lysine early in the synthesis to form imaging modules. These are coupled to targeting modules, in this case

  已经开发了实用，收敛的前列腺癌的MRI，PET和SPECT靶向前列腺特异性膜抗原（PSMA）成像剂的合成方法。在这种方法中，在合成初期，将螯合至1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸（DOTA）的金属置于赖氨酸的侧链上，以形成成像模块。它们与靶向模块偶联，在这种情况下，靶向模块由与激活的接头结合的PSMA结合尿素DCL组成。靶向分子成像剂（TMIA）的模块化方法具有明显的优势。通过尽早螯合MRI对比金属Gd，它可以兼作DOTA的保护基。可以利用标准的偶联和脱保护步骤将模块组装成肽，并且避免了需要用强酸除去的DOTA的三叔丁基保护。在最终步骤中，这可以使成像模块与多种靶向剂温和结合。进一步发现，在合成过程中，两种不稳定的金属La3 +或Ce3 +可以用作DOTA中的占位符，然后在弱酸中被PET / SPECT中使用的金属Cu2 +，Ga3 +，In3 +和Y3 +转化。这
• Synthesis and Evaluation of Gd^III-Based Magnetic Resonance Contrast Agents for Molecular Imaging of Prostate-Specific Membrane Antigen
  作者：Sangeeta Ray Banerjee、Ethel J. Ngen、Matthew W. Rotz、Samata Kakkad、Ala Lisok、Richard Pracitto、Mrudula Pullambhatla、Zhengping Chen、Tariq Shah、Dmitri Artemov、Thomas J. Meade、Zaver M. Bhujwalla、Martin G. Pomper

  DOI：10.1002/anie.201503417

  日期：2015.9.7

  Magnetic resonance (MR) imaging is advantageous because it concurrently provides anatomic, functional, and molecular information. MR molecular imaging can combine the high spatial resolution of this established clinical modality with molecular profiling in vivo. However, as a result of the intrinsically low sensitivity of MR imaging, high local concentrations of biological targets are required to generate

  磁共振成像（MR）具有优势，因为它同时提供了解剖，功能和分子信息。MR分子成像可以将这种既定临床模式的高空间分辨率与体内分子谱相结合。但是，由于MR成像固有的低灵敏度，需要高局部浓度的生物靶标才能产生可​​分辨的MR对比度。我们假设前列腺特异性膜抗原（PSMA）是前列腺癌成像和治疗的有吸引力的靶标，可以作为基于MR的分子成像的合适生物标记。我们已经合成了三种新的基于高亲和力，低分子量Gd III的PSMA靶向造影剂，其中包含一到三种Gd III 每分子螯合。我们评估了这些试剂在溶液，前列腺癌细胞和体内实验模型中的弛豫特性，以证明基于PSMA的MR分子成像的可行性。
• [EN] PSMA-TARGETING COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS CIBLANT PSMA ET LEURS UTILISATIONS
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2010108125A3

  公开（公告）日：2011-03-24
• ⁶⁴Cu-Labeled Inhibitors of Prostate-Specific Membrane Antigen for PET Imaging of Prostate Cancer
  作者：Sangeeta Ray Banerjee、Mrudula Pullambhatla、Catherine A. Foss、Sridhar Nimmagadda、Riccardo Ferdani、Carolyn J. Anderson、Ronnie C. Mease、Martin G. Pomper

  DOI：10.1021/jm401921j

  日期：2014.3.27

  Prostate-specific membrane antigen (PSMA) is a well-recognized target for identification and therapy of a variety of cancers. Here we report five (64)Cu-labeled inhibitors of PSMA, [(64)Cu]3-7, which are based on the lysine-glutamate urea scaffold and utilize a variety of macrocyclic chelators, namely NOTA(3), PCTA(4), Oxo-DO3A(5), CB-TE2A(6), and DOTA(7), in an effort to determine which provides the most suitable pharmacokinetics for in vivo PET imaging. [(64)Cu]3-7 were prepared in high radiochemical yield (60-90%) and purity (>95%). Positron emission tomography (PET) imaging studies of [(64)Cu]3-7 revealed specific accumulation in PSMA-expressing xenografts (PSMA+ PC3 PIP) relative to isogenic control tumor (PSMA- PC3 flu) and background tissue. The favorable kinetics and high image contrast provided by CB-TE2A chelated [(64)Cu]6 suggest it as the most promising among the candidates tested. That could be due to the higher stability of [(64)Cu]CB-TE2A as compared with [(64)Cu]NOTA, [(64)Cu]PCTA, [(64)Cu]Oxo-DO3A, and [(64)Cu]DOTA chelates in vivo.