(5S,12S,16S)-tri-tert-butyl 5-(4-(bis((1-methyl-1H-imidazol-2-yl)methyl)amino)butyl)-1-(9H-fluoren-9-yl)-3,6,14-trioxo-2-oxa-4,7,13,15-tetraazaoctadecane-12,16,18-tricarboxylate | 1429493-39-9

• 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: (5S,12S,16S)-tri-tert-butyl 5-(4-(bis((1-methyl-1H-imidazol-2-yl)methyl)amino)butyl)-1-(9H-fluoren-9-yl)-3,6,14-trioxo-2-oxa-4,7,13,15-tetraazaoctadecane-12,16,18-tricarboxylate
• CAS: 1429493-39-9
• 化学式: C₅₅H₇₉N₉O₁₀
• 分子量: 1026.29
• InChiKey: BXYRDDHAQHPISS-KJFLPAQCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.36
• 重原子数：
  74.0
• 可旋转键数：
  25.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  226.34
• 氢给体数：
  4.0
• 氢受体数：
  15.0

反应信息

• 作为反应物：
  描述：

  (5S,12S,16S)-tri-tert-butyl 5-(4-(bis((1-methyl-1H-imidazol-2-yl)methyl)amino)butyl)-1-(9H-fluoren-9-yl)-3,6,14-trioxo-2-oxa-4,7,13,15-tetraazaoctadecane-12,16,18-tricarboxylate 在 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以35%的产率得到(7S,14S,18S)-tri-tert-butyl 7-amino-1-(1-methyl-1H-imidazol-2-yl)-2-((1-methyl-1H-imidazol-2-yl)methyl)-8,16-dioxo-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylate
  参考文献：
  名称：

  Synthesis and SAR of 99mTc/Re-labeled small molecule prostate specific membrane antigen inhibitors with novel polar chelates

  摘要：

  Prostate specific membrane antigen (PSMA) is recognized as an attractive molecular target for the development of radiopharmaceuticals to image and potentially treat metastatic prostate cancer. A series of novel Tc-99m/Re-tricarbonyl radiolabeled PSMA inhibitors were therefore synthesized by the attachment of glutamate-urea-lysine (Glu-urea-Lys) and glutamate-urea-glutamate (Glu-urea-Glu) pharmacophore to single amino acid chelate (SAAC) where the SAAC ligand was either bis(pyridin-2-ylmethyl)amino (DPA), bis((1-methyl-1H-imidazol-2-yl)methyl)amino (NMI), bis((1-(carboxymethyl)-1H-imidazol-2-yl)methyl)amino (CIM) or bis((1-(2-(bis(carboxymethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino (TIM). The in vitro binding affinity of the rhenium complexes was evaluated using PSMA-expressing human prostate cancer LNCaP cells. IC50 values ranged from 3.8 +/- 2 to > 2000 nM. A linker between the SAAC chelate and pharmacophore was required for high affinity binding. However, extending the length of the linker did not substantially improve binding. PSMA binding was also influenced by the nature of the SAAC chelate. One of the most potent compounds, 23b (IC50 = 4.8 +/- 2.7 nM), was radiolabeled with technetium tricarbonyl ({Tc-99m(CO)(3)}(+)) to afford the {Tc-99m(CO)(3)}(+) complex in excellent yield and high purity. This effort has led to the identification of a diverse series of promising high affinity {Tc-99m(CO)(3)}(+) radiolabeled PSMA inhibitors. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.09.014
• 作为产物：
  描述：

  (S)-di-tert-butyl 2-(3-((S)-6-amino-1-(tert-butoxy)-1-oxohexan-2-yl)ureido)pentanedioate 、 (S)-2-(((9H-fluoren-9-yl)-methoxy)carbonylamino)-6-(bis((1-methyl-1H-imidazol-2-yl)-methyl)amino)hexanoic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以58%的产率得到(5S,12S,16S)-tri-tert-butyl 5-(4-(bis((1-methyl-1H-imidazol-2-yl)methyl)amino)butyl)-1-(9H-fluoren-9-yl)-3,6,14-trioxo-2-oxa-4,7,13,15-tetraazaoctadecane-12,16,18-tricarboxylate
  参考文献：
  名称：

  Synthesis and SAR of 99mTc/Re-labeled small molecule prostate specific membrane antigen inhibitors with novel polar chelates

  摘要：

  Prostate specific membrane antigen (PSMA) is recognized as an attractive molecular target for the development of radiopharmaceuticals to image and potentially treat metastatic prostate cancer. A series of novel Tc-99m/Re-tricarbonyl radiolabeled PSMA inhibitors were therefore synthesized by the attachment of glutamate-urea-lysine (Glu-urea-Lys) and glutamate-urea-glutamate (Glu-urea-Glu) pharmacophore to single amino acid chelate (SAAC) where the SAAC ligand was either bis(pyridin-2-ylmethyl)amino (DPA), bis((1-methyl-1H-imidazol-2-yl)methyl)amino (NMI), bis((1-(carboxymethyl)-1H-imidazol-2-yl)methyl)amino (CIM) or bis((1-(2-(bis(carboxymethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino (TIM). The in vitro binding affinity of the rhenium complexes was evaluated using PSMA-expressing human prostate cancer LNCaP cells. IC50 values ranged from 3.8 +/- 2 to > 2000 nM. A linker between the SAAC chelate and pharmacophore was required for high affinity binding. However, extending the length of the linker did not substantially improve binding. PSMA binding was also influenced by the nature of the SAAC chelate. One of the most potent compounds, 23b (IC50 = 4.8 +/- 2.7 nM), was radiolabeled with technetium tricarbonyl ({Tc-99m(CO)(3)}(+)) to afford the {Tc-99m(CO)(3)}(+) complex in excellent yield and high purity. This effort has led to the identification of a diverse series of promising high affinity {Tc-99m(CO)(3)}(+) radiolabeled PSMA inhibitors. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.09.014