2-(fluoromethyl)-4-(ethynyl)thiazole | 1228354-15-1

• 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-(ethynyl)thiazole
• 英文别名: 4-Ethynyl-2-(fluoromethyl)thiazole；4-ethynyl-2-(fluoromethyl)-1,3-thiazole
• CAS: 1228354-15-1
• 化学式: C₆H₄FNS
• 分子量: 141.169
• InChiKey: BEYBQCYNCYFGNF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  9
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 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-(ethynyl)thiazole 、 trans-3-bromocyclohex-2-enone o-methyl oxime 在 copper(l) iodide 、 四(三苯基膦)钯 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 以11%的产率得到(E)-3-((2-(fluoromethyl)thiazol-4-yl)ethynyl)cyclohex-2-enone O-methyl oxime
  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：

  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

文献信息

• [EN] PYRAZOLOPYRIMIDINES, A PROCESS FOR THEIR PREPARATION AND THEIR USE AS MEDICINE<br/>[FR] PYRAZOLOPYRIMIDINES, PROCÉDÉ POUR LEUR PRÉPARATION ET LEUR UTILISATION COMME MÉDICAMENT
  申请人：MERZ PHARMA GMBH & CO KGAA

  公开号：WO2010063487A1

  公开（公告）日：2010-06-10

  The invention relates to pyrazolopyrimidine derivatives as well as their pharmaceutically acceptable salts. The invention further relates to a process for the preparation of such compounds. The compounds of the invention are mGluR5 modulators and are therefore useful for the control and prevention of acute and/or chronic neurological disorders.

  该发明涉及吡唑吡咯嘧啶衍生物及其药用可接受的盐。该发明还涉及一种制备这类化合物的方法。该发明的化合物是mGluR5调节剂，因此对于控制和预防急性和/或慢性神经系统疾病非常有用。
• 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.