2,3,5,6-tetrafluorophenyl 4-isocyanobutanoate | 950887-97-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 英文名称: 2,3,5,6-tetrafluorophenyl 4-isocyanobutanoate
• CAS: 950887-97-5
• 化学式: C₁₁H₇F₄NO₂
• 分子量: 261.176
• InChiKey: XTUIVTVNVGVARJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.85
• 重原子数：
  18.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  30.66
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  2,3,5,6-tetrafluorophenyl 4-isocyanobutanoate 、 c(RGDyK) 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以50%的产率得到2-[(2S,5R,8S,11S)-11-[3-(diaminomethylideneamino)propyl]-5-[(4-hydroxyphenyl)methyl]-8-[4-(4-isocyanobutanoylamino)butyl]-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]acetic acid
  参考文献：
  名称：

  Novel 99mTc ‘4 + 1’ peptide conjugates: Tuning the biodistribution by variation of coligands

  摘要：

  A sophisticated coligand strategy is presented for peptide-derived radioconjugates based on Tc-99m '4 + 1' mixed-ligand complexes. The new pharmacologically active coligands are assessed for Tc-99m-labeling of the RGD-peptide cyclo(Arg-Gly-Asp-D-Tyr-Lys) which is an established vehicle to target alpha(v)beta(3) integrins playing a crucial part in tumor pathogenesis.Complexes of the general formula [Tc-99m(NS3R)X] were synthesized and evaluated, in which Tc(III) is coordinated by NS3R, a derivative of the tetradentate chelator 2,2',2 ''-nitrilotriethanethiol (NS3), and by X, a monodentate binding isocyanide bearing the biomolecule. The novel tetradentate chelators (NS3R = NS(3)crown, NS(3)en, NS3(COOH)(3)) constitute NS3 with a crown ether, an amine or a tricarboxylic acid as pharmacological modifiers. The isocyanides (X = L2-RGD, L2-Lys) contained the linker isocyanobutanoic acid (L2) coupled to N-6-Lys of the RGD-peptide and additionally to a single Lys.The lipophilicity (distribution coefficient log D-O/W, pH = 7.4) of the RGD-containing radiotracers decreased in the order of the coligands NS(3)crown (-1.7 +/- 0.1), NS(3)en (-2.7 +/- 0.1) and NS3(COOH)(3) (-3.3 +/- 0.1). In the same order of the coligands, the biodistribution of the series [Tc-99m(NS3R)(L2-RGD)] in normal rats showed a decrease of hepatobiliary and an increase of urinary excretion.The ratio of specifically to unspecifically uptaken activity (sum of surface bound and internalized activity) in alpha(v)beta(3) integrin-expressing M21 cells was in the range of approximately 4-5 and comparable for all [Tc-99m(NS3R)(L2-RGD)] tracers. The biodistribution of [Tc-99m(NS(3)en)(L2-RGD)] in v/v mice bearing M21 and M21L (control) tumor xenografts exhibited a specific tumor uptake with a low target-background ratio.The metabolic stability of the [Tc-99m(NS3R)(L2-RGD)] tracers in normal rats was high, since 75-87% of the radioactivity in the plasma extract was assigned to the injected radiotracers 60 min after intravenous application in a rat. The hypothetical metabolites [Tc-99m(NS3R)(L2-Lys)] were not found.These results demonstrate a considerable improvement of in vivo properties of Tc-99m '4 + 1' peptide conjugates and open up the possibility of applying the labeling approach for further radiodiagnostic peptides. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.05.010
• 作为产物：
  描述：

  2,3,5,6-tetrafluorophenyl 4-formylaminobutanoate 在 伯吉斯试剂 作用下， 以 二氯甲烷 为溶剂， 生成 2,3,5,6-tetrafluorophenyl 4-isocyanobutanoate
  参考文献：
  名称：

  评价和比较具有不同99mTc核心的99mTc标记的d-葡萄糖胺衍生物作为潜在的肿瘤显像剂

  摘要：

  异氰酸酯是一种强配位配体，可以与[ 99m Tc（I）（CO）3 ] +核芯和[ 99m Tc（I）] +核芯配位，生成稳定的99m Tc络合物，因此开发了99m Tc标记的异氰酸酯络合物单光子发射计算机断层扫描（SPECT）成像被认为是非常令人感兴趣的。为了开发具有令人满意的肿瘤吸收和体内合适的药代动力学特性的潜在肿瘤显像剂，一种新型的d-氨基葡萄糖异氰酸酯衍生物4-异氰基N-（2,4,5-三羟基-6-（羟甲基）四氢-2 H合成了吡喃-3-基丁酰胺（CN3DG），并用[ 99m Tc（I）] +和[ 99m Tc（CO）3 ] +核进行了放射性标记，获得了[ 99m Tc（CN3DG）6 ] +和[ 99m Tc（CO）3（CN3DG）3 ] +放射性标记产率高（> 95％）。两种配合物均表现出良好的亲水性和体外稳定性。在S180细胞中进行的细胞摄取研究表明，它们被葡萄糖转运蛋白转运到细

  DOI：

  10.1002/aoc.6008

文献信息

• The synthesis of a ^99mTc-labeled tetravalent targeting probe upon isonitrile coordination to ^99mTc^I for enhanced target uptake in saturable systems
  作者：Yuki Mizuno、Tomoya Uehara、Chun-wei Jen、Hiromichi Akizawa、Yasushi Arano

  DOI：10.1039/c9ra04311j

  日期：——

  The difference in 2-proton's acidity between L_β and L_G led to dramatically different results of their reactions with [^99mTc][Tc(CO)₃(OH₂)₃]⁺.

  2-质子的酸度在L_β和L_G之间的差异导致它们与[^99mTc][Tc(CO)₃(OH₂)₃]⁺反应产生截然不同的结果。
• Novel ^99mTc labelled complexes with 2-nitroimidazole isocyanide: design, synthesis and evaluation as potential tumor hypoxia imaging agents
  作者：Qing Ruan、Xuran Zhang、Xiao Lin、Xiaojiang Duan、Junbo Zhang

  DOI：10.1039/c8md00146d

  日期：——

  Radiolabelled 2-nitroimidazoles have been used for imaging hypoxia. With the aim of developing novel 99mTc radiotracers for imaging hypoxia, four novel 2-nitroimidazole isocyanide derivatives (2a, 2b, 2c, and 2d) were synthesized and radiolabelling was carried out for preparing their corresponding 99mTc complexes. These 99mTc complexes were stable in vitro and could exhibit good hypoxic selectivity

  放射性标记的 2-硝基咪唑已用于缺氧成像。为了开发用于缺氧成像的新型99m Tc放射性示踪剂，合成了四种新型2-硝基咪唑异氰化物衍生物（2a、2b、2c和2d ），并进行放射性标记以制备其相应的99m Tc配合物。这些99m Tc 配合物在体外稳定，并且具有良好的缺氧选择性。分配系数结果表明它们是亲水性的，并且对携带S180肿瘤的小鼠的生物分布评估表明所有复合物都可以在肿瘤中积聚。其中，99m Tc- 2c在注射后2小时表现出最高的肿瘤摄取以及肿瘤/血液和肿瘤/肌肉比率。此外，单光子发射计算机断层扫描 (SPECT) 成像研究表明肿瘤中存在明显的积累，表明99m Tc- 2c是缺氧成像的有希望的候选者。
• 一种标记的葡萄糖酰胺类衍生物、其制备方法、其前体及其应用
  申请人：北京师范大学

  公开号：CN116410248A

  公开（公告）日：2023-07-11

  本发明提出了一种标记的葡萄糖酰胺类衍生物、其制备方法、其前体及其应用，属于医药、化学技术领域。该葡萄糖酰胺类衍生物的通式如式Ⅰ所示。本发明所保护的上述衍生物，其整体的空间体积以及整体分子量大大下降，能够使该类衍生物的通透细胞膜磷脂层的潜力及被葡萄糖转运蛋白成功转运的潜力增强。且其在肿瘤中的滞留时间长，绝对摄取值增高，可作为一种新型的肿瘤代谢显像剂；此外，本申请开发了一种全新的前体，相对现有技术而言，合成式Ⅰ简单，并大大降低了前体的合成难度，明显增强了前体的化学稳定性，利于锝标记配合物药盒化的实现，具有重要的临床应用前景。
• Synthesis and Biological Evaluation of Novel ^99mTc-Labeled Palbociclib Derivatives Targeting Cyclin-Dependent Kinase 4/6 (CDK4/6) as Potential Cancer Imaging Agents
  作者：Xiaoqing Song、Qianqian Gan、Xuran Zhang、Junbo Zhang

  DOI：10.1021/acs.molpharmaceut.9b00540

  日期：2019.10.7

  Cancer results from cell proliferation that exceeds normal growth control. There are various specific proteins that control and regulate the cell cycle, such as cyclin-dependent kinases (CDKs), cyclins, and retinoblastoma protein (pRb). The aberration of the cyclin D-CDK4/6-INK4-pRb pathway occurs frequently in cancers; thus, CDK4/6 is an attractive target for the development of radiopharmaceuticals for tumor imaging. In this study, we chose palbociclib, which was approved by the FDA for treating ER+/HER2- advanced breast cancer as the target vector and the isonitrile group, which can coordinate strongly with the [Tc-99(m)(CO)(3)](+) core as the bifunctional chelator, to develop four novel Tc-99(m)-labeled radiotracers for tumor imaging. The ligands (L2, L3, L4, and L5) were synthesized by reacting palbociclib with isocyanide-containing active esters and then radiolabeling with a [Tc-99(m)(CO)(3)](+) core to produce radiotracers (Tc-99(m)-L2, Tc-99(m)-L3, Tc-99(m)-L4, and Tc-99(m)-L5) with high radiochemical purity (>95%) and good stability in vitro. The structures of the Tc-99(m) complexes were identified by preparation and characterization of the corresponding stable rhenium complexes. Partition coefficient results indicated that these complexes were lipophilic. A kinase inhibition assay demonstrated the high affinity of the stable Re complexes for CDK4. A cell study showed that all four complexes had substantial uptake by MCF-7 cells and could be significantly inhibited by palbociclib and nonradiolabeled ligand, indicating a CDK4/6-specific uptake mechanism. Biodistribution studies in nude mice bearing MCF-7 tumors showed that the complexes had obvious accumulation in tumors at 2 h postinjection. Tc-99(m)-L2 exhibited the highest tumor uptake and tumor/blood ratio, whereas Tc-99(m)-L4 showed the highest tumor/muscle ratio. The micro-SPECT/CT study showed that complex Tc-99(m)-L4 had visible uptake at the tumor site, and the accumulation was clearly reduced in the image after pretreatment with palbociclib, further indicating CDK4/6 specificity. All the results showed that the Tc-99(m)-labeled complexes in this work have the potential for tumor imaging.