(10S,14S)-tris(4-methoxybenzyl) 2,2-dimethyl-4,12-dioxo-3-oxa-5,11,13-triazahexadecane-10,14,16-tricarboxylate | 1045709-88-3

• 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: (10S,14S)-tris(4-methoxybenzyl) 2,2-dimethyl-4,12-dioxo-3-oxa-5,11,13-triazahexadecane-10,14,16-tricarboxylate
• CAS: 1045709-88-3
• 化学式: C₄₁H₅₃N₃O₁₂
• 分子量: 779.885
• InChiKey: MDSCNGBHEQVUSG-PXLJZGITSA-N

物化性质

• 沸点：
  881.9±65.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.75
• 重原子数：
  56.0
• 可旋转键数：
  21.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  186.05
• 氢给体数：
  3.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  (10S,14S)-tris(4-methoxybenzyl) 2,2-dimethyl-4,12-dioxo-3-oxa-5,11,13-triazahexadecane-10,14,16-tricarboxylate 以45的产率得到(S)-5-(3-((S)-1,5-bis((4-methoxybenzyl)oxy)-1,5-dioxopentan-2-yl)ureido)-6-((4-methoxybenzyl)oxy)-6-oxohexan-1-aminium tosylate
  参考文献：
  名称：

  Clin Cancer Res 2011, 17, 7645-7653

  摘要：

  DOI：
• 作为产物：
  描述：

  (4-methoxyphenyl)methyl (2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoate 在 哌啶 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.25h， 生成 (10S,14S)-tris(4-methoxybenzyl) 2,2-dimethyl-4,12-dioxo-3-oxa-5,11,13-triazahexadecane-10,14,16-tricarboxylate
  参考文献：
  名称：

  Targeted Biocompatible Nanoparticles for the Delivery of (−)-Epigallocatechin 3-Gallate to Prostate Cancer Cells

  摘要：

  Molecular targeted cancer therapy mediated by nanoparticles (NPs) is a promising strategy to overcome the lack of specificity of conventional chemotherapeutic agents. In this context, the prostate-specific membrane antigen (PSMA) has demonstrated a powerful potential for the management of prostate cancer (PCa). Cancer chemoprevention by phytochemicals is emerging as a suitable approach for the treatment of early carcinogenic processes. Since (-)-epigallocatechin 3-gallate (EGCG) has shown potent chemopreventive efficacy for PCa, we designed and developed novel targeted NPs in order to selectively deliver EGCG to cancer cells. Herein, to explore the recent concept of "nanochemoprevention", we present a study on EGCG-loaded NPs consisting of biocompatible polymers, functionalized with small molecules targeting PSMA, that exhibited a selective in vitro efficacy against PSMA-expressing PCa cells. This approach could be beneficial for high risk patients and would fulfill a significant therapeutic need, thus opening new perspectives for novel and effective treatment for PCa.

  DOI：

  10.1021/jm1013715

文献信息

• 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 Technetium-99m- and Rhenium-Labeled Inhibitors of the Prostate-Specific Membrane Antigen (PSMA)
  作者：Sangeeta R. Banerjee、Catherine A. Foss、Mark Castanares、Ronnie C. Mease、Youngjoo Byun、James J. Fox、John Hilton、Shawn E. Lupold、Alan P. Kozikowski、Martin G. Pomper

  DOI：10.1021/jm800111u

  日期：2008.8.1

  The prostate- specific membrane antigen (PSMA) is increasingly recognized as a viable target for imaging and therapy of cancer. We prepared seven 99'Tc/Re-labeled compounds by attaching known Tc/Re chelating agents to an amino-functionalized PSMA inhibitor (lys-NHCONH-glu) with or without a variable length linker moiety. Ki values ranged from 0.17 to 199 nM. Ex vivo biodistribution and in vivo imaging demonstrated the degree of specific binding to engineered PSMA+ PC3 PIP tumors. PC3-PIP cells are derived from PO that have been transduced with the gene for PSMA. Despite demonstrating nearly the lowest PSMA inhibitory potency of this series, [99`Tc(COXLI)]+ (LI = (2-pyridylmethVI)2N(CH,,)4CH(COH)NHCO-(CH2)6CO-NH-lys-NHCONH-glu) showed the highest, most selective PIP tumor uptake, at 7.9 4.0% injected dose per gram of tissue at 30 min postinjection. Radioactivity cleared from nontarget tissues to produce a PIP to flu (PSMA-PC3) ratio of 44:1 at 120 min postinjection. PSMA can accommodate the steric requirements of 99"Tc/Re complexes within PSMA inhibitors, the best results achieved with a linker moiety between the e amine of the urea lysine and the chelator.
• Development of targeted nanoparticles loaded with antiviral drugs for SARS-CoV-2 inhibition
  作者：Vanna Sanna、Sandro Satta、Tzung Hsiai、Mario Sechi

  DOI：10.1016/j.ejmech.2022.114121

  日期：2022.3
• Synthesis and Biological Evaluation of Low Molecular Weight Fluorescent Imaging Agents for the Prostate-Specific Membrane Antigen
  作者：Ying Chen、Mrudula Pullambhatla、Sangeeta R. Banerjee.、Youngjoo Byun、Marigo Stathis、Camilo Rojas、Barbara S. Slusher、Ronnie C. Mease、Martin G. Pomper

  DOI：10.1021/bc3003919

  日期：2012.12.19

  Targeted near-infrared (MR) optical imaging can be used in vivo to detect specific tissues, including malignant cells. A series of NIR fluorescent ligands targeting the prostate-specific membrane antigen (PSMA) was synthesized and each compound was tested for its ability to image PSMA+ tissues in experimental models of prostate cancer. The agents were prepared by conjugating commercially available active esters of NIR dyes, including IRDye800CW, IRDye800RS, Cy5.5, Cy7, or a derivative of indocyanine green (ICG) to the terminal amine group of (S)-2-(3-((S)-5-amino-1-carboxypentyl)ureido)pentanedioic acid 1, (14S,18S)-1-amino-8,16-dioxo-3,6-dioxa-9,15,17-triazaicosane-14,18,20-tricarboxylic acid 2 and (3S,7S)-26-amino-5,13,20-trioxo-4,6,12,21-tetraaza-hexacosane-1,3,7,22-tetracarboxylic acid 3. The K-i values for the dye-inhibitor conjugates ranged from 1 to 700 pM. All compounds proved capable of imaging PSMA+ tumors selectively to varying degrees depending on the choice of fluorophore and linker. The highest tumor uptake was observed with IRDye800CW employing a poly(ethylene glycol) or lysine suberate linker, as in 800CW-2 and 800CW-3, while the highest tumor to nontarget tissue ratios were obtained for Cy7 with these same linkers, as in Cy7-2 and Cy7-3. Compounds 2 and 3 provide useful scaffolds for targeting of PSMA+ tissues in vivo and should be useful for preparing NIR dye conjugates designed specifically for clinical intraoperative optical imaging devices.
• J. Med. Chem. 2010, 53, 1732-1740
  作者：

  DOI：——

  日期：——