5-[3-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-prop-(E)-ylidene]-5,6,7,8-tetrahydronaphthalen-1-ol | 1165451-07-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 5-[3-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-prop-(E)-ylidene]-5,6,7,8-tetrahydronaphthalen-1-ol
• 英文别名: (5E)-5-[3-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)propylidene]-7,8-dihydro-6H-naphthalen-1-ol
• CAS: 1165451-07-9
• 化学式: C₂₄H₂₉NO₃
• 分子量: 379.499
• InChiKey: WVBJAVQDPKAZMC-REZTVBANSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  41.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-[3-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-prop-(E)-ylidene]-5,6,7,8-tetrahydronaphthalen-1-ol 在 5%-palladium/activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 以90%的产率得到5-[(3-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl))propyl]-1-hydroxy-5,6,7,8-tetrahydronaphthalene
  参考文献：
  名称：

  Synthesis and Preclinical Evaluation of Novel PET Probes for P-Glycoprotein Function and Expression

  摘要：

  P-glycoprotein (P-gp) is an ATP-dependent efflux pump protecting the body against xenobiotics. A P-gp substrate (7) and an inhibitor (6) were labeled with C-11, resulting in potential tracers of P-gp function and expression. Methods: 6 and 7 were labeled using (CH3I)-C-11. C-11-verapamil was prepared as published previously, using C-11-methyl triflate. MicroPET scans (with arterial sampling) and biodistribution studies were performed in rats pretreated with saline, cyclosporin A (CsA, 50 mg/kg), or cold 6 (15 mg/kg). Results: The radiochemical yields of C-11-6 and C-11-7 were approximately 30% with a total synthesis time of 45 min. Cerebral distribution volumes (DV) of C-11-6 (2,35 +/- 0.11) and C-11-7 (1.86 +/- 0.15) in saline-treated rats were higher than or C-11-verapamil (0.64 +/- 0.12). DVs of C-11-7 and C-11-verapamil were significantly increased by CsA (to 5.26 +/- 0.14 and 5.85 +/- 0.32, respectively). The DV of C-11-6 was reduced by cold 6 (to 1.65 +/- 0.03). Its uptake was also reduced (up to 67%) in several peripheral organs that express P-gp. Conclusions: C-11-7 is a novel tracer of P-gp function with higher baseline uptake than C-11-verapamil. Upregulation of P-gp function in response to treatment (which is hard to detect with C-11-verapamil) may be detectable using C-11-7 and PET. Because C-11-6 shows specific binding in target organs, this compound is the First PET tracer allowing measurement of P-gp expression.

  DOI：

  10.1021/jm900485a
• 作为产物：
  描述：

  6,7-二甲氧基-1,2,3,4-四氢异喹啉 、 5-[3-chloro-prop-(E)-ylidene]-5,6,7,8-tetrahydro-naphthalen-1-ol 在 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 5-[3-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-prop-(E)-ylidene]-5,6,7,8-tetrahydronaphthalen-1-ol
  参考文献：
  名称：

  Synthesis and Preclinical Evaluation of Novel PET Probes for P-Glycoprotein Function and Expression

  摘要：

  P-glycoprotein (P-gp) is an ATP-dependent efflux pump protecting the body against xenobiotics. A P-gp substrate (7) and an inhibitor (6) were labeled with C-11, resulting in potential tracers of P-gp function and expression. Methods: 6 and 7 were labeled using (CH3I)-C-11. C-11-verapamil was prepared as published previously, using C-11-methyl triflate. MicroPET scans (with arterial sampling) and biodistribution studies were performed in rats pretreated with saline, cyclosporin A (CsA, 50 mg/kg), or cold 6 (15 mg/kg). Results: The radiochemical yields of C-11-6 and C-11-7 were approximately 30% with a total synthesis time of 45 min. Cerebral distribution volumes (DV) of C-11-6 (2,35 +/- 0.11) and C-11-7 (1.86 +/- 0.15) in saline-treated rats were higher than or C-11-verapamil (0.64 +/- 0.12). DVs of C-11-7 and C-11-verapamil were significantly increased by CsA (to 5.26 +/- 0.14 and 5.85 +/- 0.32, respectively). The DV of C-11-6 was reduced by cold 6 (to 1.65 +/- 0.03). Its uptake was also reduced (up to 67%) in several peripheral organs that express P-gp. Conclusions: C-11-7 is a novel tracer of P-gp function with higher baseline uptake than C-11-verapamil. Upregulation of P-gp function in response to treatment (which is hard to detect with C-11-verapamil) may be detectable using C-11-7 and PET. Because C-11-6 shows specific binding in target organs, this compound is the First PET tracer allowing measurement of P-gp expression.

  DOI：

  10.1021/jm900485a

文献信息

• Synthesis and Preclinical Evaluation of Novel PET Probes for P-Glycoprotein Function and Expression
  作者：Aren van Waarde、Nisha K. Ramakrishnan、Anna A. Rybczynska、Philip H. Elsinga、Francesco Berardi、Johan R. de Jong、Chantal Kwizera、Roberto Perrone、Mariangela Cantore、Jurgen W. A. Sijbesma、Rudi A. Dierckx、Nicola A. Colabufo

  DOI：10.1021/jm900485a

  日期：2009.7.23

  P-glycoprotein (P-gp) is an ATP-dependent efflux pump protecting the body against xenobiotics. A P-gp substrate (7) and an inhibitor (6) were labeled with C-11, resulting in potential tracers of P-gp function and expression. Methods: 6 and 7 were labeled using (CH3I)-C-11. C-11-verapamil was prepared as published previously, using C-11-methyl triflate. MicroPET scans (with arterial sampling) and biodistribution studies were performed in rats pretreated with saline, cyclosporin A (CsA, 50 mg/kg), or cold 6 (15 mg/kg). Results: The radiochemical yields of C-11-6 and C-11-7 were approximately 30% with a total synthesis time of 45 min. Cerebral distribution volumes (DV) of C-11-6 (2,35 +/- 0.11) and C-11-7 (1.86 +/- 0.15) in saline-treated rats were higher than or C-11-verapamil (0.64 +/- 0.12). DVs of C-11-7 and C-11-verapamil were significantly increased by CsA (to 5.26 +/- 0.14 and 5.85 +/- 0.32, respectively). The DV of C-11-6 was reduced by cold 6 (to 1.65 +/- 0.03). Its uptake was also reduced (up to 67%) in several peripheral organs that express P-gp. Conclusions: C-11-7 is a novel tracer of P-gp function with higher baseline uptake than C-11-verapamil. Upregulation of P-gp function in response to treatment (which is hard to detect with C-11-verapamil) may be detectable using C-11-7 and PET. Because C-11-6 shows specific binding in target organs, this compound is the First PET tracer allowing measurement of P-gp expression.