2-(tert-butyldimethylsilyloxymethyl)-4-iodothiazole | 945933-46-0

• 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-(tert-butyldimethylsilyloxymethyl)-4-iodothiazole
• 英文别名: tert-butyl-[(4-iodo-1,3-thiazol-2-yl)methoxy]-dimethylsilane
• CAS: 945933-46-0
• 化学式: C₁₀H₁₈INOSSi
• 分子量: 355.315
• InChiKey: OVXPWDKMUKHPGQ-UHFFFAOYSA-N

物化性质

• 沸点：
  307.6±22.0 °C(Predicted)
• 密度：
  1.411±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.27
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  50.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(tert-butyldimethylsilyloxymethyl)-4-iodothiazole 、 3-fluoro-5-(2-(trimethylsilyl)ethynyl)benzonitrile 在 copper(l) iodide 、 四(三苯基膦)钯 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.17h， 以20%的产率得到5-fluoro-3-(2-(2-(tert-butyldimethylsilyloxymethyl)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
• 作为产物：
  描述：

  4-bromo-2-(((tert-butyldimethylsilyl)oxy)methyl)thiazole 在 正丁基锂 、 三丁基氯化锡 、 碘 作用下， 以 乙醚 、 正己烷 、 氯仿 为溶剂， 反应 0.84h， 以230 mg的产率得到2-(tert-butyldimethylsilyloxymethyl)-4-iodothiazole
  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 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.
• J. Med. Chem. 2007, 50, 3256-3266
  作者：

  DOI：——

  日期：——