4-(3-(fluoro-18F)propyl)-2-((4-(1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenoxy)methyl)quinoline

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(3-(fluoro-18F)propyl)-2-((4-(1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenoxy)methyl)quinoline
• 英文别名: 4-(3-(18F)fluoranylpropyl)-2-[[4-(1-methyl-4-pyridin-4-ylpyrazol-3-yl)phenoxy]methyl]quinoline
• 化学式: C₂₈H₂₅FN₄O
• 分子量: 451.533
• InChiKey: OADIRORPIWSRQU-GBHUPVCCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  52.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-羟基-2-甲基喹啉 在 咪唑 、 selenium(IV) oxide 、 sodium tetrahydroborate 、 四(三苯基膦)钯 、 硼烷四氢呋喃络合物 、 potassium [¹⁸F]fluoride 、 偶氮二甲酸二叔丁酯 、 四丁基氟化铵 、 potassium carbonate 、 三乙胺 、 N,N-二异丙基乙胺 、 三苯基膦 、 4,7,13,16,21,24-六氧-1,10-二氮双环[8.8.8]二十六烷 、 lithium bromide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 53.25h， 生成 4-(3-(fluoro-18F)propyl)-2-((4-(1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenoxy)methyl)quinoline
  参考文献：
  名称：

  Synthesis of Fluorine-Containing Phosphodiesterase 10A (PDE10A) Inhibitors and the In Vivo Evaluation of F-18 Labeled PDE10A PET Tracers in Rodent and Nonhuman Primate

  摘要：

  A series of fluorine-containing PDE10A inhibitors were designed and synthesized to improve the metabolic stability of [C-11]MP-10. Twenty of the 22 new analogues had high potency and selectivity for PDE10A: 18a-j, 19d-j, 20a-b, and 21b had IC50 values <5 nM for PDE10A. Seven F-18 labeled compounds [F-18](18)a-e, [F-18]18g, and [F-18]20a were radiosynthesized by F-18-introduction onto the quinoline rather than the pyrazole moiety of the MP-10 pharmacophore and performed in vivo evaluation. Biodistribution studies in rats showed similar to 2-fold higher activity in the PDE10A-enriched striatum than nontarget brain regions; this ratio increased from 5 to 30 min postinjection, particularly for [F-18]18a-d and [F-18]20a. Micro-PET studies of [F-18]18d and [F-18]20a in nonhuman primates provided clear visualization of striatum with suitable equilibrium kinetics and favorable metabolic stability. These results suggest this strategy may identify a F-18-labeled PET tracer for quantifying the levels of PDE10A in patients with CNS disorders including Huntington's disease and schizophrenia.

  DOI：

  10.1021/acs.jmedchem.5b01205

文献信息

• Synthesis of Fluorine-Containing Phosphodiesterase 10A (PDE10A) Inhibitors and the In Vivo Evaluation of F-18 Labeled PDE10A PET Tracers in Rodent and Nonhuman Primate
  作者：Junfeng Li、Xiang Zhang、Hongjun Jin、Jinda Fan、Hubert Flores、Joel S. Perlmutter、Zhude Tu

  DOI：10.1021/acs.jmedchem.5b01205

  日期：2015.11.12

  A series of fluorine-containing PDE10A inhibitors were designed and synthesized to improve the metabolic stability of [C-11]MP-10. Twenty of the 22 new analogues had high potency and selectivity for PDE10A: 18a-j, 19d-j, 20a-b, and 21b had IC50 values <5 nM for PDE10A. Seven F-18 labeled compounds [F-18](18)a-e, [F-18]18g, and [F-18]20a were radiosynthesized by F-18-introduction onto the quinoline rather than the pyrazole moiety of the MP-10 pharmacophore and performed in vivo evaluation. Biodistribution studies in rats showed similar to 2-fold higher activity in the PDE10A-enriched striatum than nontarget brain regions; this ratio increased from 5 to 30 min postinjection, particularly for [F-18]18a-d and [F-18]20a. Micro-PET studies of [F-18]18d and [F-18]20a in nonhuman primates provided clear visualization of striatum with suitable equilibrium kinetics and favorable metabolic stability. These results suggest this strategy may identify a F-18-labeled PET tracer for quantifying the levels of PDE10A in patients with CNS disorders including Huntington's disease and schizophrenia.