2,2’-(7-(4-((2-aminoethyl)amino)-1-carboxy-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid | 1630114-57-6

• 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: 2,2’-(7-(4-((2-aminoethyl)amino)-1-carboxy-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid
• 英文别名: NH2-Noda-GA；5-(2-aminoethylamino)-2-[4,7-bis(carboxymethyl)-1,4,7-triazonan-1-yl]-5-oxopentanoic acid
• CAS: 1630114-57-6
• 化学式: C₁₇H₃₁N₅O₇
• 分子量: 417.462
• InChiKey: DTPTWBYXQVMEMQ-UHFFFAOYSA-N

物化性质

• 沸点：
  767.8±60.0 °C(Predicted)
• 密度：
  1.306±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -9.2
• 重原子数：
  29
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  177
• 氢给体数：
  5
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  2,2’-(7-(4-((2-aminoethyl)amino)-1-carboxy-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid 、 方酸二乙酯 在 sodium hydroxide 作用下， 以 aq. phosphate buffer 为溶剂， 反应 2.0h， 以93%的产率得到2-[4,7-Bis(carboxymethyl)-1,4,7-triazonan-1-yl]-5-[2-[(2-ethoxy-3,4-dioxocyclobuten-1-yl)amino]ethylamino]-5-oxopentanoic acid
  参考文献：
  名称：

  含有68Ga标记的PSMA抑制剂的方酸的合成，标记和临床前评估-与PSMA-11和PSMA-617的比较。

  摘要：

  L-赖氨酸尿素-L-谷氨酸（KuE）代表了最近针对前列腺特异性膜抗原PSMA的诊断和治疗放射性药物的关键主题。使用方酸部分将KuE与放射性标记偶联，SA的特殊结构成为该产品的功能，与PSMA-617中的芳族单元相当。在这项工作中，我们调查了方酸部分对带有KuE基序和三种典型螯合物的化合物的生物活性的影响。衍生物TRAM.SA.KuE，DOTAGA.SA.KuE和NODAGA.SA.KuE均通过直接有机反应合成，然后通过HPLC纯化。在不同温度用不同的核素标记不同量的示踪剂，包括68 Ga，44 Sc，64 Cu和177 Lu。对在右后腿有LNCaP肿瘤的NMRInu / nu裸鼠进行PET检查，包括器官的离体检查。为了比较，在相同的动物模型中还研究了68种PSMA-11和PSMA-617的Ga衍生物。

  DOI：

  10.1002/cmdc.201900559

文献信息

• MARKING PRECURSOR WITH SQUARIC ACID COUPLING
  申请人：SCV- Spezial Chemikalien Vertrieb GmbH

  公开号：US20210369877A1

  公开（公告）日：2021-12-02

  The invention relates to a marking precursor incorporating a chelator or fluorination group for radiolabelling with 44Sc, 47Sc, 55Co, 62Cu, 64Cu, 67Cu, 66Ga, 67Ga, 68Ga, 89Zr, 86Y, 90Y, 90Nb, 99mTc, 111ln, 135Sm, 140Pr, 159Gd, 149Tb, 160Tb, 161Tb, 165Er, 166Dy, 166Ho, 175Yb, 177Lu, 186Re, 188Re, 213Bi and 225Ac or with 18F, 131I or 211At, and one or two biological targeting vectors which are coupled to the chelator or fluorinating group via one or more squaric acid groups.

  该发明涉及一种包含螯合剂或氟化基团的标记前体，用于与44Sc、47Sc、55Co、62Cu、64Cu、67Cu、66Ga、67Ga、68Ga、89Zr、86Y、90Y、90Nb、99mTc、111ln、135Sm、140Pr、159Gd、149Tb、160Tb、161Tb、165Er、166Dy、166Ho、175Yb、177Lu、186Re、188Re、213Bi和225Ac或与18F、131I或211At进行放射标记，以及一个或两个生物靶向载体，通过一个或多个方酸基团与螯合剂或氟化基团偶联。
• [EN] FIBROBLAST ACTIVATION PROTEIN LIGANDS FOR TARGETED DELIVERY APPLICATIONS<br/>[FR] LIGANDS DE PROTÉINE D'ACTIVATION DES FIBROBLASTES POUR APPLICATIONS D'ADMINISTRATION CIBLÉE
  申请人：PHILOCHEM AG

  公开号：WO2021160825A1

  公开（公告）日：2021-08-19

  The present invention relates to ligands of Fibroblast Activation Protein (FAP) for the active delivery of various payloads (e.g. cytotoxic drugs, radionuclides, fluorophores, proteins and immunomodulators) at the site of disease. In particular, the present invention relates to the development of FAP ligands for targeting applications, in particular diagnostic methods and/or methods for therapy or surgery in relation to a disease or disorder, such as cancer, inflammation or another disease characterized by overexpression of FAP.

  本发明涉及纤维母细胞活化蛋白（FAP）的配体，用于在疾病部位主动传递各种有效载荷（例如细胞毒药物、放射性核素、荧光染料、蛋白质和免疫调节剂）。具体而言，本发明涉及开发用于靶向应用的FAP配体，特别是用于诊断方法和/或与疾病或疾病相关的治疗或手术方法，如癌症、炎症或另一种以FAP过表达为特征的疾病。
• Design, synthesis and in vitro evaluation of heterobivalent peptidic radioligands targeting both GRP- and VPAC1-Receptors concomitantly overexpressed on various malignancies – Is the concept feasible?
  作者：Simon Lindner、Luise Fiedler、Björn Wängler、Peter Bartenstein、Ralf Schirrmacher、Carmen Wängler

  DOI：10.1016/j.ejmech.2018.05.047

  日期：2018.7

  Radiolabeled heterobivalent peptidic ligands (HBPLs), being able to address different receptors, are highly interesting tumor imaging agents as they can offer multiple advantages over monovalent peptide receptor ligands. However, few examples of radiolabeled HBPLs have been described so far. One promising approach is the combination of gastrin-releasing peptide receptor (GRPR)- and vasoactive intestinal peptide receptor subtype 1 (VPAC(1)R)-targeting peptides into one single radioligand since gastrinomas, prostate and breast cancer have been shown to concomitantly or complementarily overexpress both receptors. Here we report the design and synthesis of different HBPLs, comprising a GRPR-binding (BBN7-14) and a VPAC(1)R-targeting (PACAP-27) peptide. The heterodimers were varied with regard to the distance between the peptide binders and the steric rigidity of the systems. We radiolabeled the HBPLs 19 23 as well as their monomeric reference standards 26 and 27 with Ga-68, achieving radiochemical yields and purities of 95-99% and non-optimized molar activities of 25-61 GBq/mu mol. We tested the stability of the radioligands and further evaluated them in vitro regarding their uptake in different prostate carcinoma cell lines (PC-3, DU-145 and VCaP cells).We found that the heterobivalent substances [Ga-68]19-[Ga-68]23 showed comparable uptakes into the tumor cells to those of the respective monomers [Ga-68]26 and [Ga-68]27, indicating that both peptides are still able to address their target receptors. Furthermore, the obtained results indicate that in case of overall low receptor densities, heterobivalent peptides surpass peptide monomers in tumor cell uptake. Most importantly, it could be shown by blocking studies that both peptide parts of the HBPL [Ga-68]19 contributed to tumor cell uptake in VCaP cells, expressing both receptor types.Thus, we describe here the first examples of HBPLs being able to address the GRPR as well as the VPAC(1)R and have the potential to - by several mechanisms improve tumor targeting for several malignancies compared to monospecific peptides. (C) 2018 Elsevier Masson SAS. All rights reserved.
• FIBROBLAST ACTIVATION PROTEIN LIGANDS FOR TARGETED DELIVERY APPLICATIONS
  申请人：Philochem AG

  公开号：EP3891138A1

  公开（公告）日：2021-10-13
• Synthesis, Labeling and Preclinical Evaluation of a Squaric Acid Containing PSMA Inhibitor Labeled with ⁶⁸ Ga: A Comparison with PSMA‐11 and PSMA‐617
  作者：Lukas Greifenstein、Nils Engelbogen、Hanane Lahnif、Jean‐Philippe Sinnes、Ralf Bergmann、Michael Bachmann、Frank Rösch

  DOI：10.1002/cmdc.201900559

  日期：2020.4.20

  radiopharmaceuticals targeting the prostate specific membrane antigen PSMA. Using a squaric acid moiety for coupling of KuE with a radioactive label, the peculiar structural of SA becomes a feature of the product comparable to aromatic units in PSMA-617. In this work, we investigate the influence of squaric acid moiety on the biological activity of the compound carrying a KuE motif and three typical chelates

  L-赖氨酸尿素-L-谷氨酸（KuE）代表了最近针对前列腺特异性膜抗原PSMA的诊断和治疗放射性药物的关键主题。使用方酸部分将KuE与放射性标记偶联，SA的特殊结构成为该产品的功能，与PSMA-617中的芳族单元相当。在这项工作中，我们调查了方酸部分对带有KuE基序和三种典型螯合物的化合物的生物活性的影响。衍生物TRAM.SA.KuE，DOTAGA.SA.KuE和NODAGA.SA.KuE均通过直接有机反应合成，然后通过HPLC纯化。在不同温度用不同的核素标记不同量的示踪剂，包括68 Ga，44 Sc，64 Cu和177 Lu。对在右后腿有LNCaP肿瘤的NMRInu / nu裸鼠进行PET检查，包括器官的离体检查。为了比较，在相同的动物模型中还研究了68种PSMA-11和PSMA-617的Ga衍生物。