{4-[2-(bis-carboxymethylamino)-5-(4-isothiocyanatophenyl) pentyl]-7-carboxymethyl-[1,4,7]triazonan-1-yl}acetic acid | 1392222-52-4

• 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: {4-[2-(bis-carboxymethylamino)-5-(4-isothiocyanatophenyl) pentyl]-7-carboxymethyl-[1,4,7]triazonan-1-yl}acetic acid
• 英文别名: {4-[2-(bis(carboxymethyl)amino)-5-(4-isothiocyanatophenyl)pentyl]-7-carboxymethyl[1,4,7]triazonan-1-yl}acetic acid；3p-C-NETA-NCS；2-[4-[2-[Bis(carboxymethyl)amino]-5-(4-isothiocyanatophenyl)pentyl]-7-(carboxymethyl)-1,4,7-triazonan-1-yl]acetic acid；2-[4-[2-[bis(carboxymethyl)amino]-5-(4-isothiocyanatophenyl)pentyl]-7-(carboxymethyl)-1,4,7-triazonan-1-yl]acetic acid
• CAS: 1392222-52-4
• 化学式: C₂₆H₃₇N₅O₈S
• 分子量: 579.674
• InChiKey: IEFJTSOWUJITSQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -6.5
• 重原子数：
  40
• 可旋转键数：
  16
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  207
• 氢给体数：
  4
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  {tert-butoxycarbonylmethyl-[1-hydroxymethyl-4-(4-nitrophenyl)butyl]amino}acetic acid tert-butyl ester 在 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 10% Pd/C 、 氢气 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 1,4-二氧六环 、 乙醇 、 氯仿 、 水 、 乙腈 为溶剂， -5.0~20.0 ℃ 、137.9 kPa 条件下， 反应 75.0h， 生成 {4-[2-(bis-carboxymethylamino)-5-(4-isothiocyanatophenyl) 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

文献信息

• 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：US20130310555A1

  公开（公告）日：2013-11-21

  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.

  通过氮杂环丙烷离子的亲核环开反应，立体选择性和区域选择性合成化合物，用于立体选择性和区域选择性合成治疗和诊断化合物。
• US9446995B2
  申请人：——

  公开号：US9446995B2

  公开（公告）日：2016-09-20
• [EN] BIMODAL LIGANDS WITH MACROCYCLIC AND ACYCLIC BINDING MOIETIES, COMPLEXES AND COMPOSITIONS THEREOF, AND METHODS OF USING<br/>[FR] LIGANDS BIMODAUX AVEC DES FRACTIONS DE LIAISON MACROCYCLIQUES ET ACYCLIQUES, COMPLEXES ET COMPOSITIONS LES COMPRENANT, ET PROCÉDÉS D'UTILISATION
  申请人：ILLINOIS TECHNOLOGY INST

  公开号：WO2010011367A2

  公开（公告）日：2010-01-28

  Substituted l,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 use in diagnostic imaging and treatment of a cellular disorder.
• Synthesis and Preclinical Evaluation of Bifunctional Ligands for Improved Chelation Chemistry of ⁹⁰Y and ¹⁷⁷Lu for Targeted Radioimmunotherapy
  作者：Chi Soo Kang、Xiang Sun、Fang Jia、Hyun A Song、Yunwei Chen、Michael Lewis、Hyun-Soon Chong

  DOI：10.1021/bc200696b

  日期：2012.9.19

  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.