[¹⁸F]-2-(2-(4'-(2-fluoroacetamido)biphenyl-4-ylsulfonyl)phenyl)acetic acid | 1427565-66-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [¹⁸F]-2-(2-(4'-(2-fluoroacetamido)biphenyl-4-ylsulfonyl)phenyl)acetic acid
• 英文别名: 2-[2-[4-[4-[(2-(18F)fluoranylacetyl)amino]phenyl]phenyl]sulfonylphenyl]acetic acid
• CAS: 1427565-66-9
• 化学式: C₂₂H₁₈FNO₅S
• 分子量: 426.455
• InChiKey: CREFCFAJHQSGNR-VNRZBHCFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-碘苯乙酸 在 potassium phosphate 、 四(三苯基膦)钯 、 oxone||potassium monopersulfate triple salt 、 2-(2-(4-bromophenylthio)phenyl)acetic acid 、 铜 、 N,N-二异丙基乙胺 、 三氟乙酸 、 potassium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 20.0~140.0 ℃ 、689.49 kPa 条件下， 反应 28.57h， 生成 [¹⁸F]-2-(2-(4'-(2-fluoroacetamido)biphenyl-4-ylsulfonyl)phenyl)acetic acid
  参考文献：
  名称：

  Synthesis and Preliminary Evaluation in Tumor Bearing Mice of New ¹⁸F-Labeled Arylsulfone Matrix Metalloproteinase Inhibitors as Tracers for Positron Emission Tomography

  摘要：

  New fluorinated, arylsulfone-based matrix metalloproteinase (MMP) inhibitors containing carboxylate as the zinc binding group were synthesized as radiotracers for positron emission tomography. Inhibitors were characterized by K-i for MMP-2 in the nanomolar range and by a fair selectivity for MMP-2/9/12/13 over MMP-1/3/14. Two of these compounds were obtained in the F-18-radiolabeled form, with radiochemical purity and yield suitable for preliminary studies in mice xenografted with a human U-87 MG glioblastoma. Target density in xenografts was assessed by Western blot, yielding B-max/K-d = 14. The biodistribution of the tracer was dominated by liver uptake and hepatobiliary clearance. Tumor uptake of F-18-labeled MMP inhibitors was about 30% that of [F-18]fluorodeoxyglucose. Accumulation of radioactivity within the tumor periphery colocalized with MMP-2 activity (evaluated by in situ zimography). However, specific tumor uptake accounted for only 18% of total uptake. The aspecific uptake was ascribed to the high binding affinity between the radiotracer and serum albumin.

  DOI：

  10.1021/jm4001743

文献信息

• Synthesis and Preliminary Evaluation in Tumor Bearing Mice of New ¹⁸F-Labeled Arylsulfone Matrix Metalloproteinase Inhibitors as Tracers for Positron Emission Tomography
  作者：Francesca Casalini、Lorenza Fugazza、Giovanna Esposito、Claudia Cabella、Chiara Brioschi、Alessia Cordaro、Luca D’Angeli、Antonietta Bartoli、Azzurra M. Filannino、Concetta V. Gringeri、Dario L. Longo、Valeria Muzio、Elisa Nuti、Elisabetta Orlandini、Gianluca Figlia、Angelo Quattrini、Lorenzo Tei、Giuseppe Digilio、Armando Rossello、Alessandro Maiocchi

  DOI：10.1021/jm4001743

  日期：2013.3.28

  New fluorinated, arylsulfone-based matrix metalloproteinase (MMP) inhibitors containing carboxylate as the zinc binding group were synthesized as radiotracers for positron emission tomography. Inhibitors were characterized by K-i for MMP-2 in the nanomolar range and by a fair selectivity for MMP-2/9/12/13 over MMP-1/3/14. Two of these compounds were obtained in the F-18-radiolabeled form, with radiochemical purity and yield suitable for preliminary studies in mice xenografted with a human U-87 MG glioblastoma. Target density in xenografts was assessed by Western blot, yielding B-max/K-d = 14. The biodistribution of the tracer was dominated by liver uptake and hepatobiliary clearance. Tumor uptake of F-18-labeled MMP inhibitors was about 30% that of [F-18]fluorodeoxyglucose. Accumulation of radioactivity within the tumor periphery colocalized with MMP-2 activity (evaluated by in situ zimography). However, specific tumor uptake accounted for only 18% of total uptake. The aspecific uptake was ascribed to the high binding affinity between the radiotracer and serum albumin.