3-((2-bromothiazol-4-yl)ethynyl)-5-fluorobenzonitrile | 1262778-34-6

• 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-bromothiazol-4-yl)ethynyl)-5-fluorobenzonitrile
• 英文别名: 3-((2-bromothiazol)-4-ethynyl)-5-fluorobenzonitrile；3-[2-(2-bromo-1,3-thiazol-4-yl)ethynyl]-5-fluorobenzonitrile
• CAS: 1262778-34-6
• 化学式: C₁₂H₄BrFN₂S
• 分子量: 307.146
• InChiKey: ABAUFLMLBRRLAN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  64.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-((2-bromothiazol-4-yl)ethynyl)-5-fluorobenzonitrile 在 4,7,13,16,21,24-六氧-1,10-二氮双环[8.8.8]二十六烷 potassium carbonate 、 氢氟酸 作用下， 以 水 、 二甲基亚砜 为溶剂， 反应 0.17h， 生成 3-((2-fluorothiazol-4-yl)ethynyl)-5-fluorobenzonitrile
  参考文献：
  名称：

  2-FLUOROTHIAZOLE DERIVATIVES USEFUL AS IMAGING AGENTS; METHODS OF SYNTHESIS, AND METHODS OF USE

  摘要：

  本文披露了一种用于成像哺乳动物大脑中代谢型谷氨酸亚型5受体（mGluR5）的Novel18F标记噻唑衍生物。本文还披露了一种合成所声称的噻唑衍生物的方法，该方法在热加热或微波条件下用于芳基硫醚，可高产得到化合物。本文还披露了使用所声称的18F标记噻唑衍生物作为成像剂的成像方法。本文还披露了卤代噻唑衍生物也可用作治疗剂。本文还披露了使用某些卤代噻唑衍生物治疗mGluR5介导的疾病的方法。

  公开号：

  US20110098326A1
• 作为产物：
  描述：

  5-氨基-3-氟苯腈 在 copper(l) iodide 、 四(三苯基膦)钯 、 亚硝酸丁酯 、 四丁基氟化铵 、 三乙胺 、 copper(I) bromide 作用下， 以 四氢呋喃 、 2-甲基-1,2-丙二醇 、 乙腈 为溶剂， 反应 0.58h， 生成 3-((2-bromothiazol-4-yl)ethynyl)-5-fluorobenzonitrile
  参考文献：
  名称：

  Syntheses of 2-Amino and 2-Halothiazole Derivatives as High-Affinity Metabotropic Glutamate Receptor Subtype 5 Ligands and Potential Radioligands for in Vivo Imaging

  摘要：

  The structure of the potent selective mGlu(5) ligand, SP203 (1, 3-fluoro-5-[[2-(fluoromethyl)thiazol-4-yl]ethynyl]benzonitrile), was modified by replacing the 2-fluoromethyl substituent with an amino or halo substituent and by variation of substituents in the distal aromatic ring to provide a series of new high-affinity mGlu(5) ligands. In this series, among the most potent ligands obtained, the 2-chlorothiazoles 7a and 7b and the 2-fluorothiazole 10b showed subnanomolar mGlu(5) affinity. 10b also displayed > 10000-fold selectivity over all other metabotropic receptor subtypes plus a wide range of other receptors and binding sites. The 2-fluorothiazoles 10a and 10b were labeled using [F-18]fluoride ion (t(1/2) = 109.7 min) in moderately high radiochemical yield to provide potential radioligands that may resist troublesome radiodefluorination during the imaging of brain mGlu(5) with position emission tomography. The iodo compound 9b has nanomolar affinity for mGlu(5) and may also serve as a lead to a potential I-123-labeled ligand for imaging brain mGlu(5) with single photon emission computed tomography.

  DOI：

  10.1021/jm101430m

文献信息

• Syntheses of 2-Amino and 2-Halothiazole Derivatives as High-Affinity Metabotropic Glutamate Receptor Subtype 5 Ligands and Potential Radioligands for in Vivo Imaging
  作者：Fabrice G. Siméon、Matthew T. Wendahl、Victor W. Pike

  DOI：10.1021/jm101430m

  日期：2011.2.10

  The structure of the potent selective mGlu(5) ligand, SP203 (1, 3-fluoro-5-[[2-(fluoromethyl)thiazol-4-yl]ethynyl]benzonitrile), was modified by replacing the 2-fluoromethyl substituent with an amino or halo substituent and by variation of substituents in the distal aromatic ring to provide a series of new high-affinity mGlu(5) ligands. In this series, among the most potent ligands obtained, the 2-chlorothiazoles 7a and 7b and the 2-fluorothiazole 10b showed subnanomolar mGlu(5) affinity. 10b also displayed > 10000-fold selectivity over all other metabotropic receptor subtypes plus a wide range of other receptors and binding sites. The 2-fluorothiazoles 10a and 10b were labeled using [F-18]fluoride ion (t(1/2) = 109.7 min) in moderately high radiochemical yield to provide potential radioligands that may resist troublesome radiodefluorination during the imaging of brain mGlu(5) with position emission tomography. The iodo compound 9b has nanomolar affinity for mGlu(5) and may also serve as a lead to a potential I-123-labeled ligand for imaging brain mGlu(5) with single photon emission computed tomography.
• 2-FLUOROTHIAZOLE DERIVATIVES USEFUL AS IMAGING AGENTS; METHODS OF SYNTHESIS, AND METHODS OF USE
  申请人：Pike Victor W.

  公开号：US20110098326A1

  公开（公告）日：2011-04-28

  Novel 18 F-labeled thiazole derivatives useful for imaging of metabotropic glutamate subtype 5 receptors (mGluR5) in living mammalian brain are disclosed herein. Also disclosed herein is a synthetic method for making the claimed thiazole derivatives under thermal heating or microwave conditions for aryl thioethers that provides the compounds in high yield. Imaging methods in which the claimed 18 F-labeled thiazole derivatives are used as imaging agents are also disclosed. Halogen substituted thiazole derivative disclosed herein are also useful as therapeutic agents. Methods of treating mGluR5 mediated disorders with certain halogen substituted thiazole derivatives are disclosed.

  本文披露了一种用于成像哺乳动物大脑中代谢型谷氨酸亚型5受体（mGluR5）的Novel18F标记噻唑衍生物。本文还披露了一种合成所声称的噻唑衍生物的方法，该方法在热加热或微波条件下用于芳基硫醚，可高产得到化合物。本文还披露了使用所声称的18F标记噻唑衍生物作为成像剂的成像方法。本文还披露了卤代噻唑衍生物也可用作治疗剂。本文还披露了使用某些卤代噻唑衍生物治疗mGluR5介导的疾病的方法。