2-[[4-(6-Fluoropyridin-2-yl)piperazin-1-yl]methyl]pyrazolo[1,5-a]pyridine | 1016167-59-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-[[4-(6-Fluoropyridin-2-yl)piperazin-1-yl]methyl]pyrazolo[1,5-a]pyridine
• CAS: 1016167-59-1
• 化学式: C₁₇H₁₈FN₅
• 分子量: 311.362
• InChiKey: CECDNRUCUZFOLS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  36.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  吡唑并[1,5-a]吡啶-2-羧醛 、 1-(6-氟-2-吡啶基)哌嗪 在 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 生成 2-[[4-(6-Fluoropyridin-2-yl)piperazin-1-yl]methyl]pyrazolo[1,5-a]pyridine
  参考文献：
  名称：

  Synthesis, Radiofluorination, and In Vitro Evaluation of Pyrazolo[1,5-a]pyridine-Based Dopamine D₄ Receptor Ligands: Discovery of an Inverse Agonist Radioligand for PET

  摘要：

  A series of fluoro-substituted analogs structurally derived from the aminomethyl-substituted pyrazolo[1,5-a]pyridine lead compounds 9 (FAUC 113) and 10 (FAUC 213) were synthesized and evaluated as high-affinity D(4) receptor (D(4)R) ligands (3a-3h, K(i) = 1.3-28 nM). The para-fluoroethoxy-substituted derivatives 3f and 3h revealed an outstanding D(4) subtype selectivity of more than 3 orders of magnitude over both congeners D(2) and D(3) combined with inverse agonism at D(4)R. The corresponding (18)F-labeled radioligands revealed high serum stability in vitro and log P values of 2-3. In vitro rat brain autoradiography showed specific binding of [(18)F]3h in distinct brain regions, including the gyrus dentate of the hippocampus, that were inhibited by both eticlopride (65-80%) and the selective D(4)R antagonist 10 (78-93%). The observed binding pattern was mainly consistent with the known D(4)R distribution in the rat brain. Thus, [(18)F]3h (FAUC F41) represents a potential radioligand for studying the D(4)R in vivo by positron emission tomography (PET).

  DOI：

  10.1021/jm701375u

文献信息

• Synthesis, Radiofluorination, and In Vitro Evaluation of Pyrazolo[1,5-<i>a</i>]pyridine-Based Dopamine D₄ Receptor Ligands: Discovery of an Inverse Agonist Radioligand for PET
  作者：Olaf Prante、Rainer Tietze、Carsten Hocke、Stefan Löber、Harald Hübner、Torsten Kuwert、Peter Gmeiner

  DOI：10.1021/jm701375u

  日期：2008.3.1

  A series of fluoro-substituted analogs structurally derived from the aminomethyl-substituted pyrazolo[1,5-a]pyridine lead compounds 9 (FAUC 113) and 10 (FAUC 213) were synthesized and evaluated as high-affinity D(4) receptor (D(4)R) ligands (3a-3h, K(i) = 1.3-28 nM). The para-fluoroethoxy-substituted derivatives 3f and 3h revealed an outstanding D(4) subtype selectivity of more than 3 orders of magnitude over both congeners D(2) and D(3) combined with inverse agonism at D(4)R. The corresponding (18)F-labeled radioligands revealed high serum stability in vitro and log P values of 2-3. In vitro rat brain autoradiography showed specific binding of [(18)F]3h in distinct brain regions, including the gyrus dentate of the hippocampus, that were inhibited by both eticlopride (65-80%) and the selective D(4)R antagonist 10 (78-93%). The observed binding pattern was mainly consistent with the known D(4)R distribution in the rat brain. Thus, [(18)F]3h (FAUC F41) represents a potential radioligand for studying the D(4)R in vivo by positron emission tomography (PET).