tert-butyl 2-[(1-{4,7-bis[2-(tert-butoxy)-2-oxoethyl]-1,4,7-triazonan-1-yl}-5-[4-nitrophenyl]pentan-2-yl)[2-(tert-butoxy)-2-oxoethyl]amino]acetate | 1258946-46-1

• 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: tert-butyl 2-[(1-{4,7-bis[2-(tert-butoxy)-2-oxoethyl]-1,4,7-triazonan-1-yl}-5-[4-nitrophenyl]pentan-2-yl)[2-(tert-butoxy)-2-oxoethyl]amino]acetate
• 英文别名: 1,1-bis[2-(tert-butoxy)-2-oxoethyl]-2-[3-(4-nitrophenyl)propyl]aziridin-1-ium perchlorate；1,1-Bis[2-(tert-butoxy)-2-oxoethyl]-2-[3-(4-nitrophenyl)propyl]aziridin-1-ium perchlorate；tert-butyl 2-[1-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-2-[3-(4-nitrophenyl)propyl]aziridin-1-ium-1-yl]acetate;perchlorate
• CAS: 1258946-46-1
• 化学式: C₂₃H₃₅N₂O₆*ClO₄
• 分子量: 534.991
• InChiKey: DFWZRVWSDOESKM-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -0.96
• 重原子数：
  36
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  173
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-[(1-{4,7-bis[2-(tert-butoxy)-2-oxoethyl]-1,4,7-triazonan-1-yl}-5-[4-nitrophenyl]pentan-2-yl)[2-(tert-butoxy)-2-oxoethyl]amino]acetate 在 10% Pd/C 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 乙腈 为溶剂， -5.0~20.0 ℃ 、137.9 kPa 条件下， 反应 38.0h， 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
• 作为产物：
  描述：

  {tert-butoxycarbonylmethyl-[1-hydroxymethyl-4-(4-nitrophenyl)butyl]amino}acetic acid tert-butyl ester 在 N-溴代丁二酰亚胺(NBS) 、 silver perchlorate 、 三苯基膦 作用下， 以 氯仿 、 乙腈 为溶剂， 反应 0.17h， 生成 tert-butyl 2-[(1-{4,7-bis[2-(tert-butoxy)-2-oxoethyl]-1,4,7-triazonan-1-yl}-5-[4-nitrophenyl]pentan-2-yl)[2-(tert-butoxy)-2-oxoethyl]amino]acetate
  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

文献信息

• Bimodal ligands with macrocyclic and acyclic binding moieties, complexes and compositions thereof, and methods of using
  申请人：Chong Hyun-soon

  公开号：US09115094B2

  公开（公告）日：2015-08-25

  Substituted 1,4,7-triazacyclononane-N,N′,N″-triacetic acid and 1,4,7,10-tetraazacyclcododecane-N,N′,N″,N′″-tetraacetic acid compounds with a pendant amino or hydroxyl group, metal complexes thereof, compositions thereof, and methods of making and use in diagnostic imaging and treatment of cellular disorders.

  用带有氨基或羟基的1,4,7-三氮杂环壬烷-N,N′,N″-三乙酸和1,4,7,10-四氮杂环十二烷-N,N′,N″,N′″-四乙酸化合物替代，以及它们的金属配合物、组合物、制备方法以及在诊断成像和治疗细胞疾病中的应用。
• [EN] MULTIFUNCTIONAL CHELATORS, COMPLEXES, AND COMPOSITIONS THEREOF, AND METHODS OF USING SAME<br/>[FR] CHÉLATEURS MULTIFONCTIONNELS, COMPLEXES, ET COMPOSITIONS DE CEUX-CI, ET LEURS PROCÉDÉS D'UTILISATION
  申请人：ILLINOIS TECHNOLOGY INST

  公开号：WO2015051362A1

  公开（公告）日：2015-04-09

  Multifunctional chelators, metal complexes thereof, compositions thereof, and methods of making and use in diagnostic imaging and treatment of cellular disorders.

  多功能螯合剂，其金属配合物，组合物以及在细胞疾病的诊断成像和治疗中的制备和使用方法。
• A highly effective bifunctional ligand for radioimmunotherapy applications
  作者：Hyun-Soon Chong、Hyun A. Song、Chi Soo Kang、Thien Le、Xiang Sun、Mamta Dadwal、Hyunbeom Lee、Xiaoli Lan、Yunwei Chen、Anzhi Dai

  DOI：10.1039/c0cc05707j

  日期：——

  A novel bifunctional ligand (3p-C-NETA) for antibody-targeted radioimmunotherapy of 90Y and 177Lu was efficiently synthesized via regiospecific ring opening of an aziridinium ion.

  一种新型的双功能配体（3p-C-NETA）用于抗体靶向的90Y和177Lu放射免疫治疗，通过特定位置的环氧乙烷离子环开合反应高效合成。
• BIMODAL LIGANDS WITH MACROCYCLIC AND ACYCLIC BINDING MOIETIES, COMPLEXES AND COMPOSITIONS THEREOF, AND METHODS OF USING
  申请人：Chong Hyun-Soon

  公开号：US20160052894A1

  公开（公告）日：2016-02-25

  Substituted 1,4,7-triazacyclononane-N,N′,N″-triacetic acid and 1,4,7,10-tetraazacycicododecane-N,N′,N″,N′″-tetraacetic acid compounds with a pendant amino or hydroxyl group, metal complexes thereof, compositions thereof, and methods of making and use in diagnostic imaging and treatment of cellular disorders.

  替代了带有氨基或羟基侧链的1,4,7-三氮杂环壬烷-N，N'，N''-三乙酸和1,4,7,10-四氮杂环十二烷-N，N'，N''，N'''-四乙酸化合物，其金属配合物，组合物以及制备和在诊断成像和治疗细胞疾病中的使用方法。
• Synthesis of therapeutic and diagnostic drugs centered on regioselective and stereoselective ring opening of aziridinium ions
  申请人：Chong Hyun-Soon

  公开号：US10189803B2

  公开（公告）日：2019-01-29

  Stereoselective and regioselective synthesis of compounds via nucleophilic ring opening reactions of aziridinium ions for use in stereoselective and regioselective synthesis of therapeutic and diagnostic compounds.

  通过氮丙啶离子的亲核开环反应立体选择性和区域选择性合成化合物，用于治疗和诊断化合物的立体选择性和区域选择性合成。