4-(methoxy-¹¹C)-2-((4-(1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenoxy)methyl)quinoline | 1607448-72-5

• 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-(methoxy-¹¹C)-2-((4-(1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenoxy)methyl)quinoline
• 英文别名: 4-(111C)methoxy-2-[[4-(1-methyl-4-pyridin-4-ylpyrazol-3-yl)phenoxy]methyl]quinoline
• CAS: 1607448-72-5
• 化学式: C₂₆H₂₂N₄O₂
• 分子量: 421.475
• InChiKey: BAKYRZWLXMZDHC-JVVVGQRLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  62.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  [11C]methyl iodide 、 2-((4-(1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenoxy)methyl)quinolin-4-ol 在 sodium hydroxide 作用下， 以 水 、 二甲基亚砜 为溶剂， 反应 0.08h， 生成 4-(methoxy-¹¹C)-2-((4-(1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenoxy)methyl)quinoline
  参考文献：
  名称：

  Radiosyntheses and in vivo evaluation of carbon-11 PET tracers for PDE10A in the brain of rodent and nonhuman primate

  摘要：

  The radiosyntheses and in vivo evaluation of four carbon-11 labeled quinoline group-containing radioligands are reported here. Radiolabeling of [C-11]1-4 was achieved by alkylation of their corresponding desmethyl precursors with [C-11]CH3I. Preliminary biodistribution evaluation in Sprague-Dawley rats demonstrated that [11C] 1 and [C-11]2 had high striatal accumulation (at peak time) for [C-11]1 and [C-11]2 were 6.0-fold and 4.5-fold at 60 min, respectively. Following MP-10 pretreatment, striatal uptake in rats of [C-11]1 and [C-11]2 was reduced, suggesting that the tracers bind specifically to PDE10A. MicroPET studies of [C-11]1 and [C-11]2 in nonhuman primates (NHP) also showed good tracer retention in the striatum with rapid clearance from non-target brain regions. Striatal uptake (SUV) of [C-11]1 reached 1.8 at 30 min with a 3.5-fold striatum: cerebellum ratio. In addition, HPLC analysis of solvent extracts from NHP plasma samples suggested that [C-11]1 had a very favorable metabolic stability. Our preclinical investigations suggest that [C-11]1 is a promising candidate for quantification of PDE10A in vivo using PET. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.03.028

文献信息

• Radiosyntheses and in vivo evaluation of carbon-11 PET tracers for PDE10A in the brain of rodent and nonhuman primate
  作者：Jinda Fan、Xiang Zhang、Junfeng Li、Hongjun Jin、Prashanth K. Padakanti、Lynne A. Jones、Hubert P. Flores、Yi Su、Joel S. Perlmutter、Zhude Tu

  DOI：10.1016/j.bmc.2014.03.028

  日期：2014.5

  The radiosyntheses and in vivo evaluation of four carbon-11 labeled quinoline group-containing radioligands are reported here. Radiolabeling of [C-11]1-4 was achieved by alkylation of their corresponding desmethyl precursors with [C-11]CH3I. Preliminary biodistribution evaluation in Sprague-Dawley rats demonstrated that [11C] 1 and [C-11]2 had high striatal accumulation (at peak time) for [C-11]1 and [C-11]2 were 6.0-fold and 4.5-fold at 60 min, respectively. Following MP-10 pretreatment, striatal uptake in rats of [C-11]1 and [C-11]2 was reduced, suggesting that the tracers bind specifically to PDE10A. MicroPET studies of [C-11]1 and [C-11]2 in nonhuman primates (NHP) also showed good tracer retention in the striatum with rapid clearance from non-target brain regions. Striatal uptake (SUV) of [C-11]1 reached 1.8 at 30 min with a 3.5-fold striatum: cerebellum ratio. In addition, HPLC analysis of solvent extracts from NHP plasma samples suggested that [C-11]1 had a very favorable metabolic stability. Our preclinical investigations suggest that [C-11]1 is a promising candidate for quantification of PDE10A in vivo using PET. (C) 2014 Elsevier Ltd. All rights reserved.