(S)-1,5-bis((4-methoxybenzyl)oxy)-1,5-dioxopentan-2-aminium chloride | 68709-64-8

• 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)-1,5-bis((4-methoxybenzyl)oxy)-1,5-dioxopentan-2-aminium chloride
• 英文别名: bis-(4-methoxybenzyl)-L-glutamate hydrochloride；bis-4-methoxybenzylglutamate hydrochloride；bis-(4-methoxybenzyl)-L-glutamate*HCl；(S)-Bis(4-methoxybenzyl) 2-aminopentanedioate hydrochloride；bis[(4-methoxyphenyl)methyl] (2S)-2-aminopentanedioate;hydrochloride
• CAS: 68709-64-8
• 化学式: C₂₁H₂₅NO₆*ClH
• 分子量: 423.894
• InChiKey: HNAVMOKVZFMXTN-FYZYNONXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.02
• 重原子数：
  29
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  97.1
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-1,5-bis((4-methoxybenzyl)oxy)-1,5-dioxopentan-2-aminium chloride 在 碳酸氢钠 、 苯甲醚 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 40.17h， 生成 (3S,7R,12R,16S)-5,14-dioxo-9,10-dithia-4,6,13,15-tetraazaoctadecane-1,3,7,12,16,18-hexacarboxylic acid
  参考文献：
  名称：

  未修饰肽与 5-18F-(三氟甲基)二苯并噻吩三氟甲磺酸盐的 18F-三氟甲基化

  摘要：

  5-(三氟甲基)-二苯并噻吩三氟甲磺酸盐的 18F 标记，通常称为 Umemoto 试剂，已通过卤素交换 18F-氟化与 18F-氟化物，然后与 Oxone 和三氟甲磺酸酐氧化环化来完成。这种新的 18F 试剂允许在硫醇半胱氨酸残基处对未修饰的肽进行直接化学选择性 18F 标记。

  DOI：

  10.1021/jacs.7b10227
• 作为产物：
  描述：

  L-谷氨酸 在 盐酸 、 四甲基胍 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.5h， 生成 (S)-1,5-bis((4-methoxybenzyl)oxy)-1,5-dioxopentan-2-aminium chloride
  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

• 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.
• Interactions between Human Glutamate Carboxypeptidase II and Urea-Based Inhibitors: Structural Characterization
  作者：Cyril Barinka、Youngjoo Byun、Crystal L. Dusich、Sangeeta R. Banerjee、Ying Chen、Mark Castanares、Alan P. Kozikowski、Ronnie C. Mease、Martin G. Pomper、Jacek Lubkowski

  DOI：10.1021/jm800765e

  日期：2008.12.25

  Urea-based, low molecular weight ligands of glutamate carboxypeptidase II (GCPII) have demonstrated efficacy in various models of neurological disorders and can serve as imaging agents for prostate cancer. To enhance further development of such compounds, we determined X-ray structures of four complexes between human GCPII and urea-based inhibitors at high resolution. All ligands demonstrate an invariant glutarate moiety within the S1' pocket of the enzyme. The ureido linkage between P1 and P1' inhibitor sites interacts with the active-site Zn(1)(2+) ion and the side chains of Tyr552 and His553. Interactions within the S1 pocket are defined primarily by a network of hydrogen bonds between the P1 carboxylate group of the inhibitors and the side chains of Arg534, Arg536, and Asn519. Importantly, we have identified a hydrophobic pocket accessory to the S1 site that can be exploited for structure-based design of novel GCPII inhibitors with increased lipophilicity.