4-cyano-N-[4-(6-chloropyrimidin-4-yl)-1,3-thiazol-2-yl]-N-methylbenzamide | 1414953-55-1

• 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: 4-cyano-N-[4-(6-chloropyrimidin-4-yl)-1,3-thiazol-2-yl]-N-methylbenzamide
• 英文别名: N-[4-(6-chloropyrimidin-4-yl)-1,3-thiazol-2-yl]-4-cyano-N-methylbenzamide
• CAS: 1414953-55-1
• 化学式: C₁₆H₁₀ClN₅OS
• 分子量: 355.807
• InChiKey: YVPXDVVXLAOJCD-UHFFFAOYSA-N

物化性质

• 熔点：
  212-214 °C
• 沸点：
  592.1±60.0 °C(predicted)
• 密度：
  1.51±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  111
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-cyano-N-[4-(6-chloropyrimidin-4-yl)-1,3-thiazol-2-yl]-N-methylbenzamide 、 异丙胺 在 potassium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 7.0h， 以61.3%的产率得到4-cyano-N-methyl-N-[4-[6-(propan-2-ylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]benzamide
  参考文献：
  名称：

  Development of N-[4-[6-(Isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methyl-4-[¹¹C]methylbenzamide for Positron Emission Tomography Imaging of Metabotropic Glutamate 1 Receptor in Monkey Brain

  摘要：

  Three novel 4-substituted benzamides have been synthesized as potential ligands for the positron emission tomography (PET) imaging of metabotropic glutamate 1 (mGlu1) receptor in the brain. Of these compounds, N-(4-(6-(isopropylamino)pyrimidin-4-yl)-1,3-thiazol-2-yl)-N,4-dimethylbenzamide (4) exhibited the highest binding affinity (K-i = 13.6 nM) for mGlu1 and was subsequently labeled with carbon-11. In vitro autoradiography using rat brain sections showed that [C-11]4 binding was consistent with the distribution of mGlu1, with high specific binding in the cerebellum and thalamus. PET studies with [C-11]4 in monkey showed a high brain uptake and a kinetic profile suitable for quantitative analysis. Pretreatment with a mGlu1-selective ligand 16 largely decreased the brain uptake, indicating high in vivo specific binding of [C-11]4 to mGlu1. In metabolite analysis, only unchanged [C-11]4 was found in the brain. [C-11]4 is a useful PET ligand for the imaging and quantitative analysis of mGlu1 in monkey brain and merits further evaluation in humans.

  DOI：

  10.1021/jm301597s
• 作为产物：
  描述：

  4-(6-氯嘧啶-4-基)-n-甲基噻唑-2-胺 、 对氰基苯甲酰氯 在 三乙胺 作用下， 以 甲苯 为溶剂， 反应 8.0h， 以67.5%的产率得到4-cyano-N-[4-(6-chloropyrimidin-4-yl)-1,3-thiazol-2-yl]-N-methylbenzamide
  参考文献：
  名称：

  Development of N-[4-[6-(Isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methyl-4-[¹¹C]methylbenzamide for Positron Emission Tomography Imaging of Metabotropic Glutamate 1 Receptor in Monkey Brain

  摘要：

  Three novel 4-substituted benzamides have been synthesized as potential ligands for the positron emission tomography (PET) imaging of metabotropic glutamate 1 (mGlu1) receptor in the brain. Of these compounds, N-(4-(6-(isopropylamino)pyrimidin-4-yl)-1,3-thiazol-2-yl)-N,4-dimethylbenzamide (4) exhibited the highest binding affinity (K-i = 13.6 nM) for mGlu1 and was subsequently labeled with carbon-11. In vitro autoradiography using rat brain sections showed that [C-11]4 binding was consistent with the distribution of mGlu1, with high specific binding in the cerebellum and thalamus. PET studies with [C-11]4 in monkey showed a high brain uptake and a kinetic profile suitable for quantitative analysis. Pretreatment with a mGlu1-selective ligand 16 largely decreased the brain uptake, indicating high in vivo specific binding of [C-11]4 to mGlu1. In metabolite analysis, only unchanged [C-11]4 was found in the brain. [C-11]4 is a useful PET ligand for the imaging and quantitative analysis of mGlu1 in monkey brain and merits further evaluation in humans.

  DOI：

  10.1021/jm301597s

文献信息

• Revisiting PFA-mediated tissue fixation chemistry: FixEL enables trapping of small molecules in the brain to visualize their distribution changes
  作者：Hiroshi Nonaka、Takeharu Mino、Seiji Sakamoto、Jae Hoon Oh、Yu Watanabe、Mamoru Ishikawa、Akihiro Tsushima、Kazuma Amaike、Shigeki Kiyonaka、Tomonori Tamura、A. Radu Aricescu、Wataru Kakegawa、Eriko Miura、Michisuke Yuzaki、Itaru Hamachi

  DOI：10.1016/j.chempr.2022.11.005

  日期：2023.2
• Development of <i>N</i>-[4-[6-(Isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-<i>N</i>-methyl-4-[¹¹C]methylbenzamide for Positron Emission Tomography Imaging of Metabotropic Glutamate 1 Receptor in Monkey Brain
  作者：Masayuki Fujinaga、Tomoteru Yamasaki、Jun Maeda、Joji Yui、Lin Xie、Yuji Nagai、Nobuki Nengaki、Akiko Hatori、Katsushi Kumata、Kazunori Kawamura、Ming-Rong Zhang

  DOI：10.1021/jm301597s

  日期：2012.12.27

  Three novel 4-substituted benzamides have been synthesized as potential ligands for the positron emission tomography (PET) imaging of metabotropic glutamate 1 (mGlu1) receptor in the brain. Of these compounds, N-(4-(6-(isopropylamino)pyrimidin-4-yl)-1,3-thiazol-2-yl)-N,4-dimethylbenzamide (4) exhibited the highest binding affinity (K-i = 13.6 nM) for mGlu1 and was subsequently labeled with carbon-11. In vitro autoradiography using rat brain sections showed that [C-11]4 binding was consistent with the distribution of mGlu1, with high specific binding in the cerebellum and thalamus. PET studies with [C-11]4 in monkey showed a high brain uptake and a kinetic profile suitable for quantitative analysis. Pretreatment with a mGlu1-selective ligand 16 largely decreased the brain uptake, indicating high in vivo specific binding of [C-11]4 to mGlu1. In metabolite analysis, only unchanged [C-11]4 was found in the brain. [C-11]4 is a useful PET ligand for the imaging and quantitative analysis of mGlu1 in monkey brain and merits further evaluation in humans.