4-(4-(4-(fluoro-18F)benzoyl)piperidin-1-yl)butyl acetate | 1598371-21-1

• 英文名称: 4-(4-(4-(fluoro-18F)benzoyl)piperidin-1-yl)butyl acetate
• CAS: 1598371-21-1
• 化学式: C₁₈H₂₄FNO₃
• 分子量: 320.393
• InChiKey: MMRQSWUHCOZIAZ-AWDFDDCISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.06
• 重原子数：
  23.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  46.61
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  4-(4-(4-(fluoro-18F)benzoyl)piperidin-1-yl)butyl acetate 在 三乙胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 0.75h， 生成 [¹⁸F]4-(4-((4-fluorophenyl)(hydroxy)(phenyl)methyl)piperidin-1-yl)butyl acetate
  参考文献：
  名称：

  Development of Fluorine-18 Labeled Metabolically Activated Tracers for Imaging of Drug Efflux Transporters with Positron Emission Tomography

  摘要：

  Increased activity of efflux transporters, e.g., P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), at the blood brain barrier is a pathological hallmark of many neurological diseases, and the resulting multiple drug resistance represents a major clinical challenge. Noninvasive imaging of transporter activity can help to clarify the underlying mechanisms of drug resistance and facilitate diagnosis, patient stratification, and treatment monitoring. We have developed a metabolically activated radiotracer for functional imaging of P-gp/BCRP activity with positron emission tomography (PET). In preclinical studies, the tracer showed excellent initial brain uptake and clean conversion to the desired metabolite, although at a sluggish rate. Blocking with P-gp/BCRP modulators led to increased levels of brain radioactivity; however, dynamic PET did not show differential clearance rates between treatment and control groups. Our results provide proof-of-concept for development of prodrug tracers for imaging of P- /BCRP function in vivo but also highlight some challenges associated with this strategy.

  DOI：

  10.1021/acs.jmedchem.5b00652
• 作为产物：
  描述：

  4-溴二苯硫醚 在 盐酸 、 正丁基锂 、 copper(II) benzoate dihydrate 、 三氟甲磺酸 、 potassium carbonate 、 potassium hydrogencarbonate 、 4,7,13,16,21,24-六氧-1,10-二氮双环[8.8.8]二十六烷 、 氢氟酸 作用下， 以 四氢呋喃 、 水 、 二甲基亚砜 、 氯苯 、 丙酮 、 乙腈 为溶剂， 反应 26.25h， 生成 4-(4-(4-(fluoro-18F)benzoyl)piperidin-1-yl)butyl acetate
  参考文献：
  名称：

  Development of Fluorine-18 Labeled Metabolically Activated Tracers for Imaging of Drug Efflux Transporters with Positron Emission Tomography

  摘要：

  Increased activity of efflux transporters, e.g., P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), at the blood brain barrier is a pathological hallmark of many neurological diseases, and the resulting multiple drug resistance represents a major clinical challenge. Noninvasive imaging of transporter activity can help to clarify the underlying mechanisms of drug resistance and facilitate diagnosis, patient stratification, and treatment monitoring. We have developed a metabolically activated radiotracer for functional imaging of P-gp/BCRP activity with positron emission tomography (PET). In preclinical studies, the tracer showed excellent initial brain uptake and clean conversion to the desired metabolite, although at a sluggish rate. Blocking with P-gp/BCRP modulators led to increased levels of brain radioactivity; however, dynamic PET did not show differential clearance rates between treatment and control groups. Our results provide proof-of-concept for development of prodrug tracers for imaging of P- /BCRP function in vivo but also highlight some challenges associated with this strategy.

  DOI：

  10.1021/acs.jmedchem.5b00652