2-[(2S,5R,8S,11S)-11-[3-(diaminomethylideneamino)propyl]-5-[(4-hydroxyphenyl)methyl]-8-[4-(4-isocyanobutanoylamino)butyl]-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]acetic acid | 1242101-08-1

• 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: 2-[(2S,5R,8S,11S)-11-[3-(diaminomethylideneamino)propyl]-5-[(4-hydroxyphenyl)methyl]-8-[4-(4-isocyanobutanoylamino)butyl]-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]acetic acid
• CAS: 1242101-08-1
• 化学式: C₃₂H₄₆N₁₀O₉
• 分子量: 714.779
• InChiKey: SOTLDFGBKJJNPT-XQUALCHDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.5
• 重原子数：
  51
• 可旋转键数：
  16
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  301
• 氢给体数：
  10
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  2,3,5,6-tetrafluorophenyl 4-isocyanobutanoate 、 c(RGDyK) 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以50%的产率得到2-[(2S,5R,8S,11S)-11-[3-(diaminomethylideneamino)propyl]-5-[(4-hydroxyphenyl)methyl]-8-[4-(4-isocyanobutanoylamino)butyl]-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]acetic 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