2-(fluoromethyl)-4-(2-(trimethylsilyl)ethynyl)thiazole | 945933-40-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(fluoromethyl)-4-(2-(trimethylsilyl)ethynyl)thiazole
• 英文别名: 2-(fluoromethyl)-4-((trimethylsilyl)ethynyl)thiazole；2-fluoromethyl-4-((trimethylsilyl)ethynyl)thiazole；2-[2-(fluoromethyl)-1,3-thiazol-4-yl]ethynyl-trimethylsilane
• CAS: 945933-40-4
• 化学式: C₉H₁₂FNSSi
• 分子量: 213.351
• InChiKey: MPSLAORBOHTBIY-UHFFFAOYSA-N

物化性质

• 熔点：
  42-44 °C
• 沸点：
  238.0±33.0 °C(Predicted)
• 密度：
  1.09±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.84
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  41.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(fluoromethyl)-4-(2-(trimethylsilyl)ethynyl)thiazole 在 四丁基氟化铵 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 2-(fluoromethyl)-4-(ethynyl)thiazole
  参考文献：
  名称：

  Syntheses and pharmacological characterization of novel thiazole derivatives as potential mGluR5 PET ligands

  摘要：

  Four novel thiazole containing ABP688 derivatives were synthesized and evaluated for their binding affinity towards the metabotropic glutamate receptor subtype 5 (mGluR5). (E)-3-((2-(Fluoromethyl)thiazol-4-yl)ethynyl)cyclohex-2-enone O-methyl oxime (FTECMO), the ligand with the highest binding affinity (K-i = 5.5 +/- 1.1 nM), was labeled with fluorine-18. [F-18]-FTECMO displayed optimal lipophilicity (log D-pH7.4 = 1.6 +/- 0.2) and high stability in rat and human plasma as well as sufficient stability in rat liver microsomes. In vitro autoradiography with [F-18]-FTECMO revealed a heterogeneous and displaceable binding in mGluR5-rich brain regions. PET imaging with [F-18]-FTECMO in Wistar rats, however, showed low brain uptake. Uptake of radioactivity into the skull was observed suggesting in vivo defluorination. Thus, although [F-18]-FTECMO is an excellent ligand for the detection of mGluR5 in vitro, its in vivo characteristics are not optimal for the imaging of mGluR5 in rats in vivo. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.070
• 作为产物：
  描述：

  1-氯-4-三甲基锡-3-丁炔-2-酮 、 2-氟乙烷硫代酰胺 以 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 以65%的产率得到2-(fluoromethyl)-4-(2-(trimethylsilyl)ethynyl)thiazole
  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

• Syntheses of mGluR5 PET radioligands through the radiofluorination of diaryliodonium tosylates
  作者：Sanjay Telu、Joong-Hyun Chun、Fabrice G. Siméon、Shuiyu Lu、Victor W. Pike

  DOI：10.1039/c1ob05555k

  日期：——

  3-Fluoro-1-((thiazol-4-yl)ethynyl)benzenes constitute an important class of high-affinity metabotropic glutamate subtype 5 receptor (mGluR5) ligands, some of which have been labeled with fluorine-18 (t1/2 = 109.7 min), to provide radioligands for molecular imaging of brain mGluR5 in living animal and human subjects with positron emission tomography (PET). Labeling in the 3-fluoro position of such ligands can be achieved through aromatic nucleophilic substitution of a halide leaving group with [18F]fluoride ion when a weakly activating m-nitrile group is present, but is generally very low yielding (<8%). Here we used a microfluidic reaction platform to show that greatly enhanced (up to 6-fold) radiochemical yields can be achieved from suitably synthesized diaryliodonium tosylate precursors. The presence of a m-nitrile or other activating group is not required. Similar conditions were adopted in a more conventional automated radiochemistry platform having a single-pot reactor, to produce mGluR5 radioligands with useful radioactivities for PET imaging.

  3-氟-1-((噻唑-4-基)乙炔基)苯系物是一类重要的高亲和性代谢谷氨酸亚型 5 受体（mGluR5）配体，其中一些已用氟-18（t1/2 = 109.7 分钟）标记，为正电子发射断层扫描（PET）对活体动物和人体脑部 mGluR5 进行分子成像提供了放射性配体。当存在弱活化间腈基团时，可通过芳香族亲核取代卤化物离去基团与[18F]氟离子来实现此类配体 3-氟位置的标记，但通常产率很低（<8%）。在这里，我们利用微流体反应平台证明，通过适当合成二芳碘对甲苯磺酸盐前体，可大大提高放射化学产率（高达 6 倍）。无需存在间腈或其他活化基团。在具有单锅反应器的更传统的自动化放射化学平台中也采用了类似的条件，以生产具有 PET 成像有用放射性活性的 mGluR5 放射性配体。
• 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.
• Syntheses and pharmacological characterization of novel thiazole derivatives as potential mGluR5 PET ligands
  作者：Cindy A. Baumann、Linjing Mu、Nicole Wertli、Stefanie D. Krämer、Michael Honer、Pius A. Schubiger、Simon M. Ametamey

  DOI：10.1016/j.bmc.2010.06.070

  日期：2010.8

  Four novel thiazole containing ABP688 derivatives were synthesized and evaluated for their binding affinity towards the metabotropic glutamate receptor subtype 5 (mGluR5). (E)-3-((2-(Fluoromethyl)thiazol-4-yl)ethynyl)cyclohex-2-enone O-methyl oxime (FTECMO), the ligand with the highest binding affinity (K-i = 5.5 +/- 1.1 nM), was labeled with fluorine-18. [F-18]-FTECMO displayed optimal lipophilicity (log D-pH7.4 = 1.6 +/- 0.2) and high stability in rat and human plasma as well as sufficient stability in rat liver microsomes. In vitro autoradiography with [F-18]-FTECMO revealed a heterogeneous and displaceable binding in mGluR5-rich brain regions. PET imaging with [F-18]-FTECMO in Wistar rats, however, showed low brain uptake. Uptake of radioactivity into the skull was observed suggesting in vivo defluorination. Thus, although [F-18]-FTECMO is an excellent ligand for the detection of mGluR5 in vitro, its in vivo characteristics are not optimal for the imaging of mGluR5 in rats in vivo. (C) 2010 Elsevier Ltd. All rights reserved.