| 1392222-50-2

• 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
• CAS: 1392222-50-2
• 化学式: C₄₁H₇₁N₅O₈
• 分子量: 762.043
• InChiKey: JGRSZTUMZYHGEU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.55
• 重原子数：
  54.0
• 可旋转键数：
  15.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  144.18
• 氢给体数：
  1.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 18.0h， 以88%的产率得到{4-[2-(bis(carboxymethyl)amino)-5-(4-aminophenyl)pentyl]-7-carboxymethyl-[1,4,7]triazonan-1-yl}acetic acid
  参考文献：
  名称：

  Synthesis and Preclinical Evaluation of Bifunctional Ligands for Improved Chelation Chemistry of ⁹⁰Y and ¹⁷⁷Lu for Targeted Radioimmunotherapy

  摘要：

  We report a practical and high-yield synthesis of a bimodal bifunctional ligand 3p-C-NETA-NCS containing the isothiocyanate group for conjugation to a tumor targeting antibody. 3p-C-NETA-NCS was conjugated to a tumor-targeting antibody, trastuzumab, and the corresponding 3p-C-NETA-trastuzumab conjugate was evaluated and compared to trastuzumab conjugates of the known bifunctional ligands C-DOTA, C-DTPA, and 3p-C-DEPA for radiolabeling kinetics with Y-90 and Lu-177. 3p-C-NETA-trastuzumab conjugate exhibited extremely rapid complexation kinetics with Y-90 and Lu-177. Y-90-3p-C-NETA-trastuzumab and Lu-177-3p-C-NETA-trastuzumab conjugates were stable in human serum for 2 weeks. A pilot biodistribution study was conducted to evaluate in vivo stability and tumor targeting of Lu-177-radiolabeled trastuzumab conjugate using nude mice bearing ZR-75-1 human breast cancer. Lu-177-3p-C-NETA-trastuzumab conjugate displayed low radioactivity level at blood (1.6%), low organ uptake (<2.2%), and high tumor-to-blood ratio (6.4) at 120 h. 3p-C-NETA possesses favorable in vitro and in vivo profiles and is an excellent bifunctional chelator that can be used for targeted RIT applications using Y-90 and Lu-177 and has the potential to replace DOTA and DTPA analogues in current clinical use.

  DOI：

  10.1021/bc200696b
• 作为产物：
  描述：

  {tert-butoxycarbonylmethyl-[1-hydroxymethyl-4-(4-nitrophenyl)butyl]amino}acetic acid tert-butyl ester 在 咪唑 、 10% Pd/C 、 氢气 、 碘 、 silver perchlorate 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， -5.0~20.0 ℃ 、137.9 kPa 条件下， 反应 43.17h， 生成
  参考文献：
  名称：

  Synthesis and Preclinical Evaluation of Bifunctional Ligands for Improved Chelation Chemistry of ⁹⁰Y and ¹⁷⁷Lu for Targeted Radioimmunotherapy

  摘要：

  We report a practical and high-yield synthesis of a bimodal bifunctional ligand 3p-C-NETA-NCS containing the isothiocyanate group for conjugation to a tumor targeting antibody. 3p-C-NETA-NCS was conjugated to a tumor-targeting antibody, trastuzumab, and the corresponding 3p-C-NETA-trastuzumab conjugate was evaluated and compared to trastuzumab conjugates of the known bifunctional ligands C-DOTA, C-DTPA, and 3p-C-DEPA for radiolabeling kinetics with Y-90 and Lu-177. 3p-C-NETA-trastuzumab conjugate exhibited extremely rapid complexation kinetics with Y-90 and Lu-177. Y-90-3p-C-NETA-trastuzumab and Lu-177-3p-C-NETA-trastuzumab conjugates were stable in human serum for 2 weeks. A pilot biodistribution study was conducted to evaluate in vivo stability and tumor targeting of Lu-177-radiolabeled trastuzumab conjugate using nude mice bearing ZR-75-1 human breast cancer. Lu-177-3p-C-NETA-trastuzumab conjugate displayed low radioactivity level at blood (1.6%), low organ uptake (<2.2%), and high tumor-to-blood ratio (6.4) at 120 h. 3p-C-NETA possesses favorable in vitro and in vivo profiles and is an excellent bifunctional chelator that can be used for targeted RIT applications using Y-90 and Lu-177 and has the potential to replace DOTA and DTPA analogues in current clinical use.

  DOI：

  10.1021/bc200696b