2-((5S,11S,14R)-15-(1-amino-3,6,9,12-tetraoxapentadecan-15-amido)-11-(3-guanidinopropyl)-14-isopropyl-12-methyl-4,7,10,13,16-pentaoxo-3,6,9,12,15-pentaaza-1(1,3)-benzenacyclohexadecaphane-5-yl)acetic acid | 1325195-99-0

• 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-((5S,11S,14R)-15-(1-amino-3,6,9,12-tetraoxapentadecan-15-amido)-11-(3-guanidinopropyl)-14-isopropyl-12-methyl-4,7,10,13,16-pentaoxo-3,6,9,12,15-pentaaza-1(1,3)-benzenacyclohexadecaphane-5-yl)acetic acid
• CAS: 1325195-99-0
• 化学式: C₃₇H₆₀N₁₀O₁₂
• 分子量: 836.943
• InChiKey: XKSINLUNLVEHNW-ALKXEMMNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.41
• 重原子数：
  59.0
• 可旋转键数：
  22.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  327.95
• 氢给体数：
  10.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  succinimidyl 6-(2-(2-sulfonatobenzaldehyde)hydrazono)nicotinate 、 2-((5S,11S,14R)-15-(1-amino-3,6,9,12-tetraoxapentadecan-15-amido)-11-(3-guanidinopropyl)-14-isopropyl-12-methyl-4,7,10,13,16-pentaoxo-3,6,9,12,15-pentaaza-1(1,3)-benzenacyclohexadecaphane-5-yl)acetic acid 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 以57.4%的产率得到
  参考文献：
  名称：

  Evaluation of ^99mTc-Labeled Cyclic RGD Peptide with a PEG₄ Linker for Thrombosis Imaging: Comparison with DMP444

  摘要：

  DMP444 is a Tc-99m-labeled cyclic RGD peptide, which has been evaluated in preclinical canine deep vein thrombosis (DVT) and pulmonary embolism (PE) models, and in patients with DVT and PE by SPECT (single photon emission computed tomography). Clinical data indicated that DMP444 is useful for imaging DVT, but it had limited utility for imaging PE in patients. To understand its clinical findings, we prepared a new radiotracer P4-DMP444 by replacing the lipophilic 6-aminocaproic acid (CA) in DMP444 with a highly water-soluble PEG(4) (15-amino-4,7,10,13-tetraoxapentadecanoic acid) linker. The objective of this study was to explore the impact of PEG(4) on biological properties (biodistribution, excretion kinetics, and capability to image thrombi) of Tc-99m radiotracer. We also used canine DVT and PE models to perform imaging studies with/without the heparin pretreatment. These studies were specifically designed to explore the impact of heparin treatment on thrombosis uptake of P4-DMP444. It was found that replacing the CA linker with PEG(4) could enhance the radiotracer clearance kinetics from blood and normal organs in both rats and dogs. The fact that P4-DMP444 and DMP444 share very similar thrombosis uptake in both DVT and PE models suggests that the PEG(4) linker has little effect on GPIIb/IIIa binding affinity of cyclic RGD peptide. Even though P4-DMP444 had less accumulation than DMP444 in the blood, heart, lungs, and muscle over the 2 h study period in both rats and dogs, the difference in PE/lung and DVT/muscle ratios is marginal, suggesting that one PEG(4) linker is not sufficient to dramatically change the contrast between thrombus and background. It is very important to note that the heparin treatment of dogs with DVT and PE resulted in dramatic decrease in accumulation of P4-DMP444 in fresh thrombi. On the basis of these results, we believe that DMP444 and P4-DMP444 are excellent radiotracers for imaging both DVT and PE, and should be used in patients without antithrombosis treatment at the time of imaging.

  DOI：

  10.1021/bc2003742