4-[4-(2-tosylethoxy)phenyl]piperazine-1-carboxylic acid t-butyl ester | 1016167-50-2

• 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: 4-[4-(2-tosylethoxy)phenyl]piperazine-1-carboxylic acid t-butyl ester
• 英文别名: Tert-butyl 4-[4-[2-(4-methylphenyl)sulfonyloxyethoxy]phenyl]piperazine-1-carboxylate
• CAS: 1016167-50-2
• 化学式: C₂₄H₃₂N₂O₆S
• 分子量: 476.594
• InChiKey: HTSWEFYREPQDKI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  93.8
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-[4-(2-tosylethoxy)phenyl]piperazine-1-carboxylic acid t-butyl ester 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 1-[4-(2-tosylethoxy)phenyl]piperazine
  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
• 作为产物：
  描述：

  1,2-双甲苯氧基乙烷 、 1-Boc-4-(4-羟基苯基)-哌嗪 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 以63%的产率得到4-[4-(2-tosylethoxy)phenyl]piperazine-1-carboxylic acid t-butyl ester
  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).