2-(3-{5-[8-(bis-pyridin-2-ylmethylamino)octanoylamino]-1-carboxypentyl}ureido)pentanedioic acid | 1045709-71-4

• 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-[8-(bis-pyridin-2-ylmethylamino)octanoylamino]-1-carboxypentyl}ureido)pentanedioic acid
• 英文别名: (2S)-2-[[(1S)-5-[8-[bis(pyridin-2-ylmethyl)amino]octanoylamino]-1-carboxypentyl]carbamoylamino]pentanedioic acid
• CAS: 1045709-71-4
• 化学式: C₃₂H₄₆N₆O₈
• 分子量: 642.753
• InChiKey: HKFJZQKZEPDUIH-SVBPBHIXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  46
• 可旋转键数：
  24
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  211
• 氢给体数：
  6
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 2-(3-{5-[8-(bis-pyridin-2-ylmethylamino)octanoylamino]-1-carboxypentyl}ureido)pentanedioic acid
  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

• LABELED INHIBITORS OF PROSTATE SPECIFIC MEMBRANE ANTIGEN (PSMA), BIOLOGICAL EVALUATION, AND USE AS IMAGING AGENTS
  申请人：Pomper Martin Gilbert

  公开号：US20110064657A1

  公开（公告）日：2011-03-17

  The prostate-specific membrane antigen (PSMA) is increasingly recognized as a viable target for imaging and therapy of cancer. Various 99mTc/Re-labeled compounds were prepared by attaching known Tc/Re chelating agents to an amino-functionalized PSMA inhibitor with or without a variable length linker moiety. Ex vivo biodistribution and in vivo imaging demonstrated the degree of specific binding to engineered PSMA+ PC3 PIP tumors.

  前列腺特异性膜抗原（PSMA）越来越被认为是癌症影像和治疗的可行靶点。通过将已知的Tc/Re螯合剂连接到具有或不具有可变长度连接单元的氨基功能化PSMA抑制剂上，制备了各种99mTc/Re标记的化合物。外体分布和体内成像证明了对工程PSMA+ PC3 PIP肿瘤的特异性结合程度。
• Labeled inhibitors of prostate specific membrane antigen (PSMA) biological evaluation, and use of imaging agents
  申请人：THE JOHNS HOPKINS UNIVERSITY

  公开号：US10039845B2

  公开（公告）日：2018-08-07

  The prostate-specific membrane antigen (PSMA) is increasingly recognized as a viable target for imaging and therapy of cancer. Various 99mTc/Re-labeled compounds were prepared by attaching known Tc/Re chelating agents to an amino-functionalized PSMA inhibitor with or without a variable length linker moiety. Ex vivo biodistribution and in vivo imaging demonstrated the degree of specific binding to engineered PSMA+ PC3 PIP tumors.

  前列腺特异性膜抗原（PSMA）越来越被认为是癌症成像和治疗的可行靶点。通过将已知的锝/铼螯合剂连接到带有或不带有可变长度连接分子的氨基功能化 PSMA 抑制剂上，制备出了各种 99mTc/Re 标记化合物。体内外生物分布和体内成像显示了与PSMA+ PC3 PIP肿瘤的特异性结合程度。
• LABELED INHIBITORS OF PROSTATE SPECIFIC MEMBRANE ANTIGEN (PSMA) BIOLOGICAL EVALUATION, AND USE OF IMAGING AGENTS
  申请人：THE JOHNS HOPKINS UNIVERSITY

  公开号：US20180085478A1

  公开（公告）日：2018-03-29

  The prostate-specific membrane antigen (PSMA) is increasingly recognized as a viable target for imaging and therapy of cancer. Various 99mTc/Re-labeled compounds were prepared by attaching known Tc/Re chelating agents to an amino-functionalized PSMA inhibitor with or without a variable length linker moiety. Ex vivo biodistribution and in vivo imaging demonstrated the degree of specific binding to engineered PSMA+ PC3 PIP tumors.
• US9044468B2
  申请人：——

  公开号：US9044468B2

  公开（公告）日：2015-06-02