(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-6-(4-isocyanobutanoylamino)hexanoic acid | 1246928-25-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-6-(4-isocyanobutanoylamino)hexanoic acid
• CAS: 1246928-25-5
• 化学式: C₂₆H₂₉N₃O₅
• 分子量: 463.533
• InChiKey: NHNRMYSIUFTXAX-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  34
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  109
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-6-(4-isocyanobutanoylamino)hexanoic acid 在 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 (2S)-2-amino-6-(4-isocyanobutanoylamino)hexanoic acid
  参考文献：
  名称：

  Novel 99mTc ‘4 + 1’ peptide conjugates: Tuning the biodistribution by variation of coligands

  摘要：

  A sophisticated coligand strategy is presented for peptide-derived radioconjugates based on Tc-99m '4 + 1' mixed-ligand complexes. The new pharmacologically active coligands are assessed for Tc-99m-labeling of the RGD-peptide cyclo(Arg-Gly-Asp-D-Tyr-Lys) which is an established vehicle to target alpha(v)beta(3) integrins playing a crucial part in tumor pathogenesis.Complexes of the general formula [Tc-99m(NS3R)X] were synthesized and evaluated, in which Tc(III) is coordinated by NS3R, a derivative of the tetradentate chelator 2,2',2 ''-nitrilotriethanethiol (NS3), and by X, a monodentate binding isocyanide bearing the biomolecule. The novel tetradentate chelators (NS3R = NS(3)crown, NS(3)en, NS3(COOH)(3)) constitute NS3 with a crown ether, an amine or a tricarboxylic acid as pharmacological modifiers. The isocyanides (X = L2-RGD, L2-Lys) contained the linker isocyanobutanoic acid (L2) coupled to N-6-Lys of the RGD-peptide and additionally to a single Lys.The lipophilicity (distribution coefficient log D-O/W, pH = 7.4) of the RGD-containing radiotracers decreased in the order of the coligands NS(3)crown (-1.7 +/- 0.1), NS(3)en (-2.7 +/- 0.1) and NS3(COOH)(3) (-3.3 +/- 0.1). In the same order of the coligands, the biodistribution of the series [Tc-99m(NS3R)(L2-RGD)] in normal rats showed a decrease of hepatobiliary and an increase of urinary excretion.The ratio of specifically to unspecifically uptaken activity (sum of surface bound and internalized activity) in alpha(v)beta(3) integrin-expressing M21 cells was in the range of approximately 4-5 and comparable for all [Tc-99m(NS3R)(L2-RGD)] tracers. The biodistribution of [Tc-99m(NS(3)en)(L2-RGD)] in v/v mice bearing M21 and M21L (control) tumor xenografts exhibited a specific tumor uptake with a low target-background ratio.The metabolic stability of the [Tc-99m(NS3R)(L2-RGD)] tracers in normal rats was high, since 75-87% of the radioactivity in the plasma extract was assigned to the injected radiotracers 60 min after intravenous application in a rat. The hypothetical metabolites [Tc-99m(NS3R)(L2-Lys)] were not found.These results demonstrate a considerable improvement of in vivo properties of Tc-99m '4 + 1' peptide conjugates and open up the possibility of applying the labeling approach for further radiodiagnostic peptides. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.05.010
• 作为产物：
  描述：

  2,3,5,6-tetrafluorophenyl 4-isocyanobutanoate 、 FMOC-赖氨酸 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 (2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-6-(4-isocyanobutanoylamino)hexanoic acid
  参考文献：
  名称：

  Novel 99mTc ‘4 + 1’ peptide conjugates: Tuning the biodistribution by variation of coligands

  摘要：

  A sophisticated coligand strategy is presented for peptide-derived radioconjugates based on Tc-99m '4 + 1' mixed-ligand complexes. The new pharmacologically active coligands are assessed for Tc-99m-labeling of the RGD-peptide cyclo(Arg-Gly-Asp-D-Tyr-Lys) which is an established vehicle to target alpha(v)beta(3) integrins playing a crucial part in tumor pathogenesis.Complexes of the general formula [Tc-99m(NS3R)X] were synthesized and evaluated, in which Tc(III) is coordinated by NS3R, a derivative of the tetradentate chelator 2,2',2 ''-nitrilotriethanethiol (NS3), and by X, a monodentate binding isocyanide bearing the biomolecule. The novel tetradentate chelators (NS3R = NS(3)crown, NS(3)en, NS3(COOH)(3)) constitute NS3 with a crown ether, an amine or a tricarboxylic acid as pharmacological modifiers. The isocyanides (X = L2-RGD, L2-Lys) contained the linker isocyanobutanoic acid (L2) coupled to N-6-Lys of the RGD-peptide and additionally to a single Lys.The lipophilicity (distribution coefficient log D-O/W, pH = 7.4) of the RGD-containing radiotracers decreased in the order of the coligands NS(3)crown (-1.7 +/- 0.1), NS(3)en (-2.7 +/- 0.1) and NS3(COOH)(3) (-3.3 +/- 0.1). In the same order of the coligands, the biodistribution of the series [Tc-99m(NS3R)(L2-RGD)] in normal rats showed a decrease of hepatobiliary and an increase of urinary excretion.The ratio of specifically to unspecifically uptaken activity (sum of surface bound and internalized activity) in alpha(v)beta(3) integrin-expressing M21 cells was in the range of approximately 4-5 and comparable for all [Tc-99m(NS3R)(L2-RGD)] tracers. The biodistribution of [Tc-99m(NS(3)en)(L2-RGD)] in v/v mice bearing M21 and M21L (control) tumor xenografts exhibited a specific tumor uptake with a low target-background ratio.The metabolic stability of the [Tc-99m(NS3R)(L2-RGD)] tracers in normal rats was high, since 75-87% of the radioactivity in the plasma extract was assigned to the injected radiotracers 60 min after intravenous application in a rat. The hypothetical metabolites [Tc-99m(NS3R)(L2-Lys)] were not found.These results demonstrate a considerable improvement of in vivo properties of Tc-99m '4 + 1' peptide conjugates and open up the possibility of applying the labeling approach for further radiodiagnostic peptides. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.05.010