4-(3-fluoroazetidin-1-yl)-7-methyl-5-(1-methyl-5-(4-(trifluoromethyl)phenyl)-1H-pyrazol-4-yl)imidazo[1,5-f][1,2,4]triazine | 1394034-05-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(3-fluoroazetidin-1-yl)-7-methyl-5-(1-methyl-5-(4-(trifluoromethyl)phenyl)-1H-pyrazol-4-yl)imidazo[1,5-f][1,2,4]triazine
• 英文别名: PF-05270430；4-(3-fluoroazetidin-1-yl)-7-methyl-5-{1-methyl-5-[4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl}imidazo[5,1-f][1,2,4]triazine；Imidazo(5,1-F)(1,2,4)triazine, 4-(3-fluoro-1-azetidinyl)-7-methyl-5-(1-methyl-5-(4-(trifluoromethyl)phenyl)-1H-pyrazol-4-yl)-；4-(3-fluoroazetidin-1-yl)-7-methyl-5-[1-methyl-5-[4-(trifluoromethyl)phenyl]pyrazol-4-yl]imidazo[5,1-f][1,2,4]triazine
• CAS: 1394034-05-9
• 化学式: C₂₀H₁₇F₄N₇
• 分子量: 431.395
• InChiKey: NXNPDXUSIAPGFQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  64.1
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  5-(5-bromo-1-methyl-1H-pyrazol-4-yl)-7-methylimidazo-[5,1-f ][1,2,4]triazin-4(3H)-one 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 4-(3-fluoroazetidin-1-yl)-7-methyl-5-(1-methyl-5-(4-(trifluoromethyl)phenyl)-1H-pyrazol-4-yl)imidazo[1,5-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

• Imidazo[5,1-f][1,2,4]Triazines for the Treatment of Neurological Disorders
  申请人：HELAL Christopher John

  公开号：US20120214791A1

  公开（公告）日：2012-08-23

  The present invention relates to compounds of the Formula and pharmaceutically acceptable salts thereof, to processes for the preparation of, intermediates used in the preparation of, and compositions containing such compounds and the uses of such compounds as a method for the treatment of a disease or condition selected from the group consisting of central nervous system disorders, cognitive disorders, schizophrenia, dementia and other disorders in a mammal.

  本发明涉及公式的化合物及其药用盐，以及用于制备、用于制备的中间体、含有这些化合物的组合物和这些化合物的用途作为治疗哺乳动物中的中枢神经系统紊乱、认知障碍、精神分裂症、痴呆症和其他疾病或症状的方法。
• Imidazo[5,1-f][1,2,4]Triazines For The Treatment of Neurological Disorders
  申请人：Pfizer Inc.

  公开号：US20140066622A1

  公开（公告）日：2014-03-06

  The present invention relates to compounds of the Formula and pharmaceutically acceptable salts thereof, to processes for the preparation of, intermediates used in the preparation of, and compositions containing such compounds and the uses of such compounds as a method for the treatment of a disease or condition selected from the group consisting of central nervous system disorders, cognitive disorders, schizophrenia, dementia and other disorders in a mammal.

  本发明涉及公式的化合物及其药学上可接受的盐，制备该化合物的过程中使用的中间体，含有该化合物的组合物以及将该化合物用作哺乳动物中治疗中枢神经系统疾病、认知障碍、精神分裂症、痴呆症和其他疾病或症状的方法。
• US8598155B2
  申请人：——

  公开号：US8598155B2

  公开（公告）日：2013-12-03
• US9200000B2
  申请人：——

  公开号：US9200000B2

  公开（公告）日：2015-12-01