3-(2-(2-(fluoromethyl)thiazol-4-yl)ethynyl)benzonitrile

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(2-(2-(fluoromethyl)thiazol-4-yl)ethynyl)benzonitrile
• 英文别名: 3-[2-[2-(fluoromethyl)-1,3-thiazol-4-yl]ethynyl]benzonitrile
• 化学式: C₁₃H₇FN₂S
• 分子量: 242.276
• InChiKey: SAUAOCKTTMVEHF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  64.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-(fluoromethyl)-4-(2-(trimethylsilyl)ethynyl)thiazole 、 间溴苯甲腈 在 copper(l) iodide 、 四(三苯基膦)钯 四丁基氟化铵 、 三乙胺 作用下， 以 四氢呋喃 、 乙二醇二甲醚 为溶剂， 以56%的产率得到3-(2-(2-(fluoromethyl)thiazol-4-yl)ethynyl)benzonitrile
  参考文献：
  名称：

  Synthesis and Simple ¹⁸F-Labeling of 3-Fluoro-5-(2-(2-(fluoromethyl)thiazol-4-yl)ethynyl)benzonitrile as a High Affinity Radioligand for Imaging Monkey Brain Metabotropic Glutamate Subtype-5 Receptors with Positron Emission Tomography

  摘要：

  2-Fluoromethyl analogs of (3-[(2-methyl-1,3-thiazol-4yl)ethynyl]pyridine) were synthesized as potential ligands for metabotropic glutamate subtype-5 receptors (mGluR5s). One of these, namely, 3-fluoro-5-(2-(2-(fluoromethyl)thiazol-4-yl)ethynyl)benzonitrile (3), was found to have exceptionally high affinity (IC50 = 36 pM) and potency in a phosphoinositol hydrolysis assay (IC50 = 0.714 pM) for mGluR5. Compound 3 was labeled with fluorine-18 (t(1/2) = 109.7 min) in high radiochemical yield (87%) by treatment of its synthesized bromomethyl analog (17) with [F-18]fluoride ion and its radioligand behavior was assessed with positron emission tomography (PET). Following intravenous injection of [F-18]3 into rhesus monkey, radioactivity was avidly taken up into brain with high uptake in mGluR5 receptor-rich regions such as striata. [F-18]3 was stable in monkey plasma and human whole blood in vitro and in monkey and human brain homogenates. In monkey in vivo, a single polar radiometabolite of [F-18]3 appeared rapidly in plasma. [F-18]3 merits further evaluation as a PET radioligand for mGluR5 in human subjects.

  DOI：

  10.1021/jm0701268

文献信息

• Synthesis and Simple ¹⁸F-Labeling of 3-Fluoro-5-(2-(2-(fluoromethyl)thiazol-4-yl)ethynyl)benzonitrile as a High Affinity Radioligand for Imaging Monkey Brain Metabotropic Glutamate Subtype-5 Receptors with Positron Emission Tomography
  作者：Fabrice G. Siméon、Amira K. Brown、Sami S. Zoghbi、Velvet M. Patterson、Robert B. Innis、Victor W. Pike

  DOI：10.1021/jm0701268

  日期：2007.7.1

  2-Fluoromethyl analogs of (3-[(2-methyl-1,3-thiazol-4yl)ethynyl]pyridine) were synthesized as potential ligands for metabotropic glutamate subtype-5 receptors (mGluR5s). One of these, namely, 3-fluoro-5-(2-(2-(fluoromethyl)thiazol-4-yl)ethynyl)benzonitrile (3), was found to have exceptionally high affinity (IC50 = 36 pM) and potency in a phosphoinositol hydrolysis assay (IC50 = 0.714 pM) for mGluR5. Compound 3 was labeled with fluorine-18 (t(1/2) = 109.7 min) in high radiochemical yield (87%) by treatment of its synthesized bromomethyl analog (17) with [F-18]fluoride ion and its radioligand behavior was assessed with positron emission tomography (PET). Following intravenous injection of [F-18]3 into rhesus monkey, radioactivity was avidly taken up into brain with high uptake in mGluR5 receptor-rich regions such as striata. [F-18]3 was stable in monkey plasma and human whole blood in vitro and in monkey and human brain homogenates. In monkey in vivo, a single polar radiometabolite of [F-18]3 appeared rapidly in plasma. [F-18]3 merits further evaluation as a PET radioligand for mGluR5 in human subjects.