2-{3-[5-[7-(2,5-dioxopyrrolidin-1-yloxycarbonyl)heptanoylamino]-1-(4-methoxybenzyloxycarbonyl)pentyl]ureido}pentanedioic acid bis-(4-methoxybenzyl) ester | 1045709-75-8

• 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: 2-{3-[5-[7-(2,5-dioxopyrrolidin-1-yloxycarbonyl)heptanoylamino]-1-(4-methoxybenzyloxycarbonyl)pentyl]ureido}pentanedioic acid bis-(4-methoxybenzyl) ester
• 英文别名: bis[(4-methoxyphenyl)methyl] (2S)-2-[[(2S)-6-[[8-(2,5-dioxopyrrolidin-1-yl)oxy-8-oxooctanoyl]amino]-1-[(4-methoxyphenyl)methoxy]-1-oxohexan-2-yl]carbamoylamino]pentanedioate
• CAS: 1045709-75-8
• 化学式: C₄₈H₆₀N₄O₁₅
• 分子量: 933.022
• InChiKey: PIBYWLVLQLQKLP-ZAQUEYBZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  67
• 可旋转键数：
  33
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  241
• 氢给体数：
  3
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  (2S)-2-amino-6-[bis(quinolin-2-ylmethyl)amino]hexanoic acid 、 2-{3-[5-[7-(2,5-dioxopyrrolidin-1-yloxycarbonyl)heptanoylamino]-1-(4-methoxybenzyloxycarbonyl)pentyl]ureido}pentanedioic acid bis-(4-methoxybenzyl) ester 在 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Synthesis and Evaluation of Technetium-99m- and Rhenium-Labeled Inhibitors of the Prostate-Specific Membrane Antigen (PSMA)

  摘要：

  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.

  DOI：

  10.1021/jm800111u
• 作为产物：
  描述：

  2-{3-[1-p-methoxybenzylcarboxylate-(5-aminopentyl)]ureido}-di-p-methoxybenzyl pentanedioate 、 双琥珀酰亚胺辛二酸酯 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以56.6%的产率得到2-{3-[5-[7-(2,5-dioxopyrrolidin-1-yloxycarbonyl)heptanoylamino]-1-(4-methoxybenzyloxycarbonyl)pentyl]ureido}pentanedioic acid bis-(4-methoxybenzyl) ester
  参考文献：
  名称：

  Synthesis and Evaluation of Technetium-99m- and Rhenium-Labeled Inhibitors of the Prostate-Specific Membrane Antigen (PSMA)

  摘要：

  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.

  DOI：

  10.1021/jm800111u

文献信息

• PSMA-TARGETING COMPOUNDS AND USES THEREOF
  申请人：Pomper Martin

  公开号：US20120009121A1

  公开（公告）日：2012-01-12

  Prostate-specific membrane antigen (PSMA) targeting compounds are described. Uses of the compounds for imaging, therapy, cell sorting, and tumor mapping are also described.

  介绍了针对前列腺特异性膜抗原（PSMA）的靶向化合物。还介绍了该化合物用于成像、治疗、细胞分选和肿瘤映射的用途。
• [EN] PSMA-TARGETING COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS CIBLANT PSMA ET LEURS UTILISATIONS
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2010108125A3

  公开（公告）日：2011-03-24
• ⁶⁸Ga-Labeled Inhibitors of Prostate-Specific Membrane Antigen (PSMA) for Imaging Prostate Cancer
  作者：Sangeeta Ray Banerjee、Mrudula Pullambhatla、Youngjoo Byun、Sridhar Nimmagadda、Gilbert Green、James J. Fox、Andrew Horti、Ronnie C. Mease、Martin G. Pomper

  DOI：10.1021/jm100623e

  日期：2010.7.22

  Gallium-68 is a generator-produced radionuclide for positron emission tomography (PET) that is being increasingly used for radiolabeling of tumor-targeting peptides. Compounds [Ga-68]3 and [Ga-68]6 are high-affinity urea-based inhibitors of the prostate-specific membrane antigen (PSMA) that were synthesized in decay-uncorrected yields ranging from 60% to 70% and radiochemical purities of more than 99%. Compound [Ga-68]3 demonstrated 3.78 +/- 0.90% injected dose per gram of tissue (%ID/g) within PSMA + PIP tumor at 30 min postinjection, while [Ga-68]6 showed a 2 h PSMA + PIP tumor uptake value of 3.29 +/- 0.77 %ID/g. Target (PSMA + PIP) to nontarget (PSMA - flu) ratios were 4.6 and 18.3, respectively, at those time points. Both compounds delineated tumor clearly by small animal PET. The urea series of imaging agents for PSMA can be radiolabeled with Ga-68, a cyclotron-free isotope useful for clinical PET studies, with maintenance of target specificity.
• Urea-based peptide compounds useful for detecting inter alia prostate cancer
  申请人：The Johns Hopkins University

  公开号：EP2408755B1

  公开（公告）日：2017-05-03
• US9056841B2
  申请人：——

  公开号：US9056841B2

  公开（公告）日：2015-06-16