三氟乙酸盐 | 1269794-89-9

• 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
• 中文名称: 三氟乙酸盐
• 英文名称: (S)-5-carboxy-5-(3-((S)-1,3-dicarboxypropyl)ureido)pentan-1-amine trifluoroacetate salt
• 英文别名: 2-{[(5-amino-1-carboxypentyl)carbamoyl]amino}pentanedioic acid；(2S)-2-(3-((S)-5-amino-1-carboxypentyl)ureido)pentanedioic acid TFA；DCL；Gcpii-IN-1 tfa；(2S)-2-[[(1S)-5-amino-1-carboxypentyl]carbamoylamino]pentanedioic acid;2,2,2-trifluoroacetic acid
• CAS: 1269794-89-9
• 化学式: C₂HF₃O₂*C₁₂H₂₁N₃O₇
• 分子量: 433.339
• InChiKey: FNWDAQBGACVZNV-WSZWBAFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.18
• 重原子数：
  29
• 可旋转键数：
  11
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  216
• 氢给体数：
  7
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  三氟乙酸盐 在 copper(ll) sulfate pentahydrate 、 bathophenanthrolinedisulfonic acid disodium salt hydrate 、 碳酸氢钠 、 sodium ascorbate 作用下， 以 四氢呋喃 、 水 、 二甲基亚砜 为溶剂， 生成 (((S)-1-carboxy-5-(4-((4-((2-(2-(4-(2-fluoroethyl)phenoxy)ethoxy)ethoxy)methyl)-1H-1,2,3-triazol-1-yl)methyl)benzamido)pentyl)carbamoyl)-L-glutamic acid
  参考文献：
  名称：

  基于叠氮-炔惠斯根环加成的模块化医学成像剂：用于前列腺癌成像的 18 种 F 标记的 PSMA 示踪剂的合成和临床前评估。

  摘要：

  自从 Rolf Huisgen 在开发 1,3-偶极化合物的 [3+2] 环加成反应方面做出了开创性贡献以来，其叠氮化物-炔烃变体已成为材料科学和化学生物学中众多有机合成和生物正交过程的关键步骤。在本研究中，铜（I）催化的叠氮化物-炔环加成被应用于开发模块化分子平台，用于使用正电子发射断层扫描进行前列腺特异性膜抗原（PSMA）的医学成像。这一过程从分子设计、合成自动化和体外研究，一直到氟 18 标记 PSMA 靶向“F-PSMA-MIC”放射性示踪剂的临床前体内评估 (t 1/2 =109.7分钟）。临床前数据表明，模块化 PSMA 支架与临床使用的 [ 68 Ga]PSMA-11 具有相似的结合亲和力和成像特性。此外，我们证明，通过 [3+2] 环加成促进 PSMA 中的芳烃结合，可以提高结合亲和力，这通过分子模型得到了合理化。这里提出的 PSMA 结合支架可能有助于与其他医学成像部分轻

  DOI：

  10.1002/chem.202001795
• 作为产物：
  描述：

  N-Ε-苄氧羰基-L-赖氨酸叔丁酯盐酸盐 在 palladium 10% on activated carbon 、 甲酸铵 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 48.58h， 生成 三氟乙酸盐
  参考文献：
  名称：

  基于叠氮-炔惠斯根环加成的模块化医学成像剂：用于前列腺癌成像的 18 种 F 标记的 PSMA 示踪剂的合成和临床前评估。

  摘要：

  自从 Rolf Huisgen 在开发 1,3-偶极化合物的 [3+2] 环加成反应方面做出了开创性贡献以来，其叠氮化物-炔烃变体已成为材料科学和化学生物学中众多有机合成和生物正交过程的关键步骤。在本研究中，铜（I）催化的叠氮化物-炔环加成被应用于开发模块化分子平台，用于使用正电子发射断层扫描进行前列腺特异性膜抗原（PSMA）的医学成像。这一过程从分子设计、合成自动化和体外研究，一直到氟 18 标记 PSMA 靶向“F-PSMA-MIC”放射性示踪剂的临床前体内评估 (t 1/2 =109.7分钟）。临床前数据表明，模块化 PSMA 支架与临床使用的 [ 68 Ga]PSMA-11 具有相似的结合亲和力和成像特性。此外，我们证明，通过 [3+2] 环加成促进 PSMA 中的芳烃结合，可以提高结合亲和力，这通过分子模型得到了合理化。这里提出的 PSMA 结合支架可能有助于与其他医学成像部分轻

  DOI：

  10.1002/chem.202001795

文献信息

• The efficiency of ¹⁸F labelling of a prostate specific membrane antigen ligand <i>via</i> strain-promoted azide–alkyne reaction: reaction speed <i>versus</i> hydrophilicity
  作者：Mengzhe Wang、Christopher D. McNitt、Hui Wang、Xiaofen Ma、Sarah M. Scarry、Zhanhong Wu、Vladimir V. Popik、Zibo Li

  DOI：10.1039/c8cc03999b

  日期：——

  Here we report the 18F labeling of a prostate specific membrane antigen (PSMA) ligand via a strain promoted oxa-dibenzocyclooctyne (ODIBO)- or bicyclo[6.1.0]nonyne (BCN)-azide reaction. Although ODIBO reacts with azide 20 fold faster than BCN, in vivo PET imaging suggests that 18F-BCN-azide-PSMA demonstrated much higher tumor uptake and a much higher tumor to background contrast.

  在这里，我们报告通过应变促进的氧杂二苯并环辛炔（ODIBO）-或双环[6.1.0]壬炔（BCN）-叠氮化物反应对前列腺特异性膜抗原（PSMA）配体进行18 F标记。尽管ODIBO与叠氮化物的反应速度比BCN快20倍，但体内PET成像显示18 F- BCN-叠氮化物-PSMA表现出更高的肿瘤吸收率和更高的肿瘤与背景对比。
• [EN] NEAR-INFRARED CYANINE DYES AND CONJUGATES THEREOF<br/>[FR] COLORANTS CYANINE PROCHES INFRAROUGES ET CONJUGUÉS ASSOCIÉS
  申请人：BRACCO IMAGING SPA

  公开号：WO2021259899A1

  公开（公告）日：2021-12-30

  The present invention relates to the field of optical imaging. More particularly, it relates to compounds of the cyanine family with near- infrared emission characterized by improved physico-chemical and biological properties and to conjugates with biological ligands thereof. The invention also relates to the use of these compounds as optical diagnostic agents in imaging or therapy of solid tumors, to the methods for their preparation and to the compositions comprising them. The compounds have formula (I), formula (I), wherein X is direct bond or -O-; Y is a group selected from linear or branched C1-C6 alkyl, C3-C7 cycloalkyl and heterocyclyl, substituted by at least two hydroxyl groups; R1 and R2 are each independently a linear or branched C1-C6 alkyl substituted by a group selected from -SO3H, -COOH, -CONH2 and - COO-C1-C6 alkyl; and R3 is hydrogen, -SO3H or a linear or branched C1-C6 alkyl substituted by -COOH or -CONH-Y, wherein Y is a group selected from linear or branched C1-C6 alkyl, C3-C7 cycloalkyl and heterocyclyl, substituted by at least two hydroxyl groups.

  本发明涉及光学成像领域，更特别地，涉及靠近红外发射的靛青家族化合物，其具有改善的物理化学和生物学性质，并与生物配体共轭。本发明还涉及将这些化合物用作固体肿瘤的光学诊断剂的用途，以及其制备方法和包含它们的组合物。该化合物具有公式(I)，其中X是直接键或-O-；Y是从线性或支链C1-C6烷基，C3-C7环烷基和杂环基中选择的一个基团，该基团至少被两个羟基取代；R1和R2各自独立地是一个线性或支链C1-C6烷基，被从-SO3H，-COOH，-CONH2和-COO-C1-C6烷基中选择的一个基团取代；R3是氢，-SO3H或一个线性或支链C1-C6烷基，被-COOH或-CONH-Y取代，其中Y是从线性或支链C1-C6烷基，C3-C7环烷基和杂环基中选择的一个基团，该基团至少被两个羟基取代。
• A Series of PSMA-Targeted Near-Infrared Fluorescent Imaging Agents
  作者：Ying Chen、Il Minn、Steven P. Rowe、Alla Lisok、Samit Chatterjee、Mary Brummet、Sangeeta Ray Banerjee、Ronnie C. Mease、Martin G. Pomper

  DOI：10.3390/biom12030405

  日期：——

  We have synthesized a series of 10 new, PSMA-targeted, near-infrared imaging agents intended for use in vivo for fluorescence-guided surgery (FGS). Compounds were synthesized from the commercially available amine-reactive active NHS ester of DyLight800. We altered the linker between the PSMA-targeting urea moiety and the fluorophore with a view to improve the pharmacokinetics. Chemical yields for the conjugates ranged from 51% to 86%. The Ki values ranged from 0.10 to 2.19 nM. Inclusion of an N-bromobenzyl substituent at the ε-amino group of lysine enhanced PSMA+ PIP tumor uptake, as did hydrophilic substituents within the linker. The presence of a polyethylene glycol chain within the linker markedly decreased renal uptake. In particular, DyLight800-10 demonstrated high specific uptake relative to background signal within kidney, confirmed by immunohistochemistry. These compounds may be useful for FGS in prostate, renal or other PSMA-expressing cancers.

  我们合成了一系列10种新的、PSMA靶向的、近红外成像试剂，旨在用于体内荧光引导手术（FGS）。化合物是从商业上可得的DyLight800的胺反应性活性NHS酯合成的。我们改变了PSMA靶向尿素基团和荧光团之间的连接器，以期改善药代动力学。共轭物的化学收率在51%至86%之间。Ki值在0.10至2.19 nM之间。在赖氨酸的ε-氨基上包含N-溴苯甲基取代基增强了PSMA+ PIP肿瘤的摄取，连接器内的亲水取代基也有同样作用。连接器内的聚乙二醇链明显降低了肾脏的摄取。特别是DyLight800-10在肾脏内相对于背景信号具有高的特异性摄取，经免疫组织化学证实。这些化合物可能对前列腺、肾脏或其他PSMA表达癌症的FGS有用。
• [¹⁸F]Fluorobenzoyllysinepentanedioic Acid Carbamates: New Scaffolds for Positron Emission Tomography (PET) Imaging of Prostate-Specific Membrane Antigen (PSMA)
  作者：Xing Yang、Ronnie C. Mease、Mrudula Pullambhatla、Ala Lisok、Ying Chen、Catherine A. Foss、Yuchuan Wang、Hassan Shallal、Hannah Edelman、Adam T. Hoye、Giorgio Attardo、Sridhar Nimmagadda、Martin G. Pomper

  DOI：10.1021/acs.jmedchem.5b01268

  日期：2016.1.14

  Radiolabeled urea-based low-molecular weight inhibitors of the prostate-specific membrane antigen (PSMA) are under intense investigation as imaging and therapeutic agents for prostate and other cancers. In an effort to provide agents with less nontarget organ uptake than the ureas, we synthesized four F-18-labeled inhibitors of PSMA based on carbamate scaffolds. 4-Bromo-2-[F-18]fluorobenzoyllysineoxypentanedioic acid (OPA) carbamate [F-18]23 and 4-iodo-2-[F-18]fluorobenzoyllysine OPA carbamate [F-18]24 in particular exhibited high target-selective uptake in PSMA+ PC3 PIP tumor xenografts, with tumor-to-kidney ratios of >1 by 4 h postinjection, an important benchmark. Because of its high tumor uptake (90% injected dose per gram of tissue at 2 h postinjection) and high tumor-to-organ ratios, [F-18]23 is promising for clinical translation. Prolonged tumor-specific uptake demonstrated by [F-18]24, which did not reach equilibrium during the 4 h study period, suggests carbamates as alternative scaffolds for mitigating dose to nontarget tissues.
• A Series of Halogenated Heterodimeric Inhibitors of Prostate Specific Membrane Antigen (PSMA) as Radiolabeled Probes for Targeting Prostate Cancer
  作者：K. P. Maresca、S. M. Hillier、F. J. Femia、D. Keith、C. Barone、J. L. Joyal、C. N. Zimmerman、A. P. Kozikowski、J. A. Barrett、W. C. Eckelman、J. W. Babich

  DOI：10.1021/jm800994j

  日期：2009.1.22

  Prostate specific membrane antigen (PSMA) is a validated molecular marker for prostate cancer. A series of glutamate-urea (Glu-urea-X) heterodimeric inhibitors of PSMA were designed and synthesized where X = epsilon-N-(o-I, m-I, p-I, p-Br, o-C1, m-C1, p-C1, p-F, H)-benzyl-Lys and epsilon-(p-I, p-Br, p-C1, p-F, H)-phenylureido-Lys. The affinities for PSMA were determined by screening in a competitive binding assay. PSMA binding of the benzyllysine series was significantly affected by the nature of the halogen substituent (IC50 values, Cl < I = Br << F = H) and the ring position of the halogen atom (IC50 values, p-I < o-I << m-I). The halogen atom had little affect oil the binding affinity in the para substituted phenylureido-Lys series. Two lead iodine compounds were radiolabeled with I-123 and I-131 and demonstrated specific PSMA binding on human prostate cancer cells, warranting evaluation as radioligands for the detection, staging, and monitoring of prostate cancer.