5-[5-(4-Chloro-2-fluorophenyl)-1-methylpyrazol-4-yl]-4-(3-fluoroazetidin-1-yl)-7-methylimidazo[5,1-f][1,2,4]triazine | 1449202-12-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-[5-(4-Chloro-2-fluorophenyl)-1-methylpyrazol-4-yl]-4-(3-fluoroazetidin-1-yl)-7-methylimidazo[5,1-f][1,2,4]triazine
• 英文别名: 5-[5-(4-chloro-2-fluorophenyl)-1-methylpyrazol-4-yl]-4-(3-fluoroazetidin-1-yl)-7-methylimidazo[5,1-f][1,2,4]triazine
• CAS: 1449202-12-3
• 化学式: C₁₉H₁₆ClF₂N₇
• 分子量: 415.833
• InChiKey: VCXMTDDYFFTSOD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  64.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-氯-2-氟苯硼酸 在 1H-1,2,4-三唑 、 potassium phosphate 、 三乙胺 、 三氯氧磷 作用下， 以 乙醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 28.33h， 生成 5-[5-(4-Chloro-2-fluorophenyl)-1-methylpyrazol-4-yl]-4-(3-fluoroazetidin-1-yl)-7-methylimidazo[5,1-f][1,2,4]triazine
  参考文献：
  名称：

  Design and Selection Parameters to Accelerate the Discovery of Novel Central Nervous System Positron Emission Tomography (PET) Ligands and Their Application in the Development of a Novel Phosphodiesterase 2A PET Ligand

  摘要：

  To accelerate the discovery of novel small molecule central nervous system (CNS) positron emission tomography (PET) ligands, we aimed to define a property space that would facilitate ligand design and prioritization, thereby providing a higher probability of success for novel PET ligand development. Toward this end, we built a database consisting of 62 PET ligands that have successfully reached the clinic and IS radioligands that failed in late-stage development as negative controls. A systematic analysis of these ligands identified a set of preferred parameters for physicochemical properties, brain permeability, and nonspecific binding (NSB). These preferred parameters have subsequently been applied to several programs and have led to the successful development of novel PET ligands with reduced resources and timelines. This strategy is illustrated here by the discovery of the novel phosphodiesterase 2A (PDE2A) PET ligand 4-(3-[F-18]fluoroazetidin-1-yl)-7methyl-5-{1-methyl-5-[4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl}imidazo[5,1-f][1,2,4]triazine, [F-18]PF-05270430 (5).

  DOI：

  10.1021/jm400312y

文献信息

• Design and Selection Parameters to Accelerate the Discovery of Novel Central Nervous System Positron Emission Tomography (PET) Ligands and Their Application in the Development of a Novel Phosphodiesterase 2A PET Ligand
  作者：Lei Zhang、Anabella Villalobos、Elizabeth M. Beck、Thomas Bocan、Thomas A. Chappie、Laigao Chen、Sarah Grimwood、Steven D. Heck、Christopher J. Helal、Xinjun Hou、John M. Humphrey、Jiemin Lu、Marc B. Skaddan、Timothy J. McCarthy、Patrick R. Verhoest、Travis T. Wager、Kenneth Zasadny

  DOI：10.1021/jm400312y

  日期：2013.6.13

  To accelerate the discovery of novel small molecule central nervous system (CNS) positron emission tomography (PET) ligands, we aimed to define a property space that would facilitate ligand design and prioritization, thereby providing a higher probability of success for novel PET ligand development. Toward this end, we built a database consisting of 62 PET ligands that have successfully reached the clinic and IS radioligands that failed in late-stage development as negative controls. A systematic analysis of these ligands identified a set of preferred parameters for physicochemical properties, brain permeability, and nonspecific binding (NSB). These preferred parameters have subsequently been applied to several programs and have led to the successful development of novel PET ligands with reduced resources and timelines. This strategy is illustrated here by the discovery of the novel phosphodiesterase 2A (PDE2A) PET ligand 4-(3-[F-18]fluoroazetidin-1-yl)-7methyl-5-1-methyl-5-[4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl}imidazo[5,1-f][1,2,4]triazine, [F-18]PF-05270430 (5).