7-[(N-ethyl-4-fluoroanilino)methyl]-2-methyl-3-(pyrimidin-5-yl)-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 7-[(N-ethyl-4-fluoroanilino)methyl]-2-methyl-3-(pyrimidin-5-yl)-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one
• 英文别名: 7-((ethyl(4-fluorophenyl)amino)methyl)-2-methyl-3-(pyrimidin-5-yl)-5H-thiazolo[3,2-a]pyrimidin-5-one；7-[(N-ethyl-4-fluoro-anilino)methyl]-2-methyl-3-pyrimidin-5-yl-thiazolo[3,2-a]pyrimidin-5-one；7-[(N-ethyl-4-fluoroanilino)methyl]-2-methyl-3-pyrimidin-5-yl-[1,3]thiazolo[3,2-a]pyrimidin-5-one
• 化学式: C₂₀H₁₈FN₅OS
• 分子量: 395.46
• InChiKey: FTVBSUKOMCKIJE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  87
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  N-乙基-4-氟苯胺 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium carbonate 、 potassium carbonate 、 sodium iodide 作用下， 以 水 、 乙腈 为溶剂， 反应 5.33h， 生成 7-[(N-ethyl-4-fluoroanilino)methyl]-2-methyl-3-(pyrimidin-5-yl)-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one
  参考文献：
  名称：

  Discovery of GluN2A-Selective NMDA Receptor Positive Allosteric Modulators (PAMs): Tuning Deactivation Kinetics via Structure-Based Design

  摘要：

  The N-methyl-D-aspartate receptor (NMDAR) is a Na+ and Ca2+ permeable ionotropic glutamate receptor that is activated by the coagonists glycine and glutamate. NMDARs are critical to synaptic signaling and plasticity, and their dysfunction has been implicated in a number of neurological disorders, including schizophrenia, depression, and Alzheimer's disease. Herein we describe the discovery of potent GluN2A-selective NMDAR positive allosteric modulators (PAMs) starting from a high-throughput screening hit. Using structure-based design, we sought to increase potency at the GluN2A subtype, while improving selectivity against related amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). The structure activity relationship of channel deactivation kinetics was studied using a combination of electrophysiology and protein crystallography. Effective incorporation of these strategies resulted in the discovery of GNE-0723 (46), a highly potent and brain penetrant GluN2A-selective NMDAR PAM suitable for in vivo characterization.

  DOI：

  10.1021/acs.jmedchem.5b02010

文献信息

• [EN] THIAZOLOPYRIMIDINONES AS MODULATORS OF NMDA RECEPTOR ACTIVITY<br/>[FR] THIAZOLOPYRIMIDINONES EN TANT QUE MODULATEURS DE L'ACTIVITÉ DU RÉCEPTEUR NMDA
  申请人：HOFFMANN LA ROCHE

  公开号：WO2015052226A1

  公开（公告）日：2015-04-16

  The present invention relates to certain thiazolopyrimidinone compounds for use in modulating NMDA receptor activity, pharmaceutical compositions comprising such compounds and methods of treating neurological and psychiatric conditions.

  本发明涉及某些噻唑吡咯嘧啶酮化合物，用于调节NMDA受体活性，包括这些化合物的药物组合物以及治疗神经和精神疾病的方法。
• THIAZOLOPYRIMIDINONES AND METHODS OF USE THEREOF
  申请人：Genentech, Inc.

  公开号：US20160222033A1

  公开（公告）日：2016-08-04

  The present invention relates to certain thiazolopyrimidinone compounds, pharmaceutical compositions comprising such compounds, and methods of treatment using such compounds.

  本发明涉及某些噻唑嘧啶酮化合物、包含该类化合物的制药组合物以及使用该类化合物的治疗方法。
• Thiazolopyrimidinones and methods of use thereof
  申请人：Genentech, Inc.

  公开号：US10647731B2

  公开（公告）日：2020-05-12

  The present invention relates to certain thiazolopyrimidinone compounds, pharmaceutical compositions comprising such compounds, and methods of treatment using such compounds.

  本发明涉及某些噻唑并嘧啶酮化合物、包含此类化合物的药物组合物以及使用此类化合物进行治疗的方法。
• THIAZOLOPYRIMIDINONES AS MODULATORS OF NMDA RECEPTOR ACTIVITY
  申请人：F. Hoffmann-La Roche AG

  公开号：EP3055315B1

  公开（公告）日：2018-07-25
• US9988400B2
  申请人：——

  公开号：US9988400B2

  公开（公告）日：2018-06-05