2-{3-[1-p-methoxybenzylcarboxylate-(5-aminopentyl)]ureido}-di-p-methoxybenzyl pentanedioate | 1045709-74-7

• 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-[1-p-methoxybenzylcarboxylate-(5-aminopentyl)]ureido}-di-p-methoxybenzyl pentanedioate
• 英文别名: bis[(4-methoxyphenyl)methyl] (2S)-2-[[(2S)-6-amino-1-[(4-methoxyphenyl)methoxy]-1-oxohexan-2-yl]carbamoylamino]pentanedioate
• CAS: 1045709-74-7
• 化学式: C₃₆H₄₅N₃O₁₀
• 分子量: 679.767
• InChiKey: UQCFKQFKWWLOJO-ACHIHNKUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  49
• 可旋转键数：
  23
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  174
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  2-{3-[1-p-methoxybenzylcarboxylate-(5-aminopentyl)]ureido}-di-p-methoxybenzyl pentanedioate 、 1-[[4-(三丁基锡烷基)苯甲酰基]氧基]-2,5-吡咯烷二酮 在 三乙胺 、 N-氯代丁二酰亚胺 、 sodium iodide 、 溶剂黄146 作用下， 以 二氯甲烷 、 甲醇 为溶剂， 反应 2.33h， 生成 C₄₃H₄₈⁽¹²⁵⁾IN₃O₁₁
  参考文献：
  名称：

  Radiohalogenated Prostate-Specific Membrane Antigen (PSMA)-Based Ureas as Imaging Agents for Prostate Cancer

  摘要：

  To extend our development of new imaging agents targeting the prostate-specific membrane antigen (PSMA), we have used the versatile intermediate 2-[3-(5-amino-1-carboxy-pentyl)-ureido]-pentanedioic acid (Lys-C(O)-Glu), which allows ready incorporation of radiohalogens for single photon emission computed tomography (SPECT) and positron emission tomography (PET). We prepared 2-[3-[1-carboxy-5-(4-[I-125]iodobenzoylamino)-pentyl]-ureido]-pentanedioic acid ([I-125]3), 2-[3-[1-carboxy-5-(4-[F-18]fluoro-benzoylamino)-pentyl-ureido]-pentanedioic acid ([F-18]6), and 2-(3-[1-carboxy-5-[(5-[I-125]iodo-pyridine-3-carbonyl)-amino]-pentyl ureido)-pentanedioic acid ([I-125]8) in 65-80% (nondecay-corrected), 30-35% (decay corrected), and 59-75% (nondecay-corrected) radiochemical yields. Compound [I-125]3 demonstrated 8.8 +/- 4.7% injected close per gram (%ID/g) within PSMA(+) PC-3 PIP tumor at 30 min postinjection, which persisted, with clear delineation of the tumor by SPECT. similar tumor uptake values at early time points were demonstrated for [F-18]6 (using PET) and [I-125]8. Because of the many radiohalogenated moieties that call be attached via the e amino group, the intermediate Lys-C(O)-Glu is an attractive template upon which to develop new imaging agents for prostate cancer.

  DOI：

  10.1021/jm801055h
• 作为产物：
  描述：

  (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 在 碳酸氢钠 作用下， 以 二氯甲烷 、 水 为溶剂， 以52.5%的产率得到2-{3-[1-p-methoxybenzylcarboxylate-(5-aminopentyl)]ureido}-di-p-methoxybenzyl pentanedioate
  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：The Johns Hopkins University

  公开号：EP3222617A1

  公开（公告）日：2017-09-27

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

  介绍了前列腺特异性膜抗原（PSMA）靶向化合物。还介绍了这些化合物在成像、治疗、细胞分拣和肿瘤绘图方面的用途。
• 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