7-(4-methyl-1H-imidazol-1-yl)-2-(2-{2-[2-(trifluoromethyl)-1,3-thiazol-4-yl]phenoxy}ethyl)-3,4-dihydro-2H-pyrido[1,2-a]pyrazine-1,6-dione | 1402001-96-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 7-(4-methyl-1H-imidazol-1-yl)-2-(2-{2-[2-(trifluoromethyl)-1,3-thiazol-4-yl]phenoxy}ethyl)-3,4-dihydro-2H-pyrido[1,2-a]pyrazine-1,6-dione
• 英文别名: 7-(4-methylimidazol-1-yl)-2-[2-[2-[2-(trifluoromethyl)-1,3-thiazol-4-yl]phenoxy]ethyl]-3,4-dihydropyrido[1,2-a]pyrazine-1,6-dione
• CAS: 1402001-96-0
• 化学式: C₂₄H₂₀F₃N₅O₃S
• 分子量: 515.516
• InChiKey: AHERSACVYXVWEK-UHFFFAOYSA-N

物化性质

• 沸点：
  731.2±70.0 °C(predicted)
• 密度：
  1.48±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  109
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-[2-(trifluoromethyl)-1,3-thiazol-4-yl]phenol 、 2-(2-chloroethyl)-7-(4-methyl-1H-imidazol-1-yl)-3,4-dihydro-2H-pyrido[1,2-a]pyrazine-1,6-dione 在 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 生成 7-(4-methyl-1H-imidazol-1-yl)-2-(2-{2-[2-(trifluoromethyl)-1,3-thiazol-4-yl]phenoxy}ethyl)-3,4-dihydro-2H-pyrido[1,2-a]pyrazine-1,6-dione
  参考文献：
  名称：

  Design of Pyridopyrazine-1,6-dione γ-Secretase Modulators that Align Potency, MDR Efflux Ratio, and Metabolic Stability

  摘要：

  Herein we describe the design and synthesis of a series of pyridopyrazine-1,6-dione gamma-secretase modulators (GSMs) for Alzheimer's disease (AD) that achieve good alignment of potency, metabolic stability, and low MDR efflux ratios, while also maintaining favorable physicochemical properties. Specifically, incorporation of fluorine enabled design of metabolically less liable lipophilic alkyl substituents to increase potency without compromising the sp(3)-character. The lead compound 21 (PF-06442609) displayed a favorable rodent pharmacokinetic profile, and robust reductions of brain A beta 42 and A beta 40 were observed in a guinea pig time-course experiment.

  DOI：

  10.1021/acsmedchemlett.5b00070

文献信息

• Novel Bicyclic Pyridinones
  申请人：Pettersson Martin Youngjin

  公开号：US20120252758A1

  公开（公告）日：2012-10-04

  Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I as defined herein. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

  所述化合物及其药用可接受的盐被披露，其中所述化合物具有如本文所定义的Formula I的结构。相应的药物组合物、治疗方法、合成方法和中间体也被披露。
• NOVEL BICYCLIC PYRIDINONES
  申请人：Pfizer Inc.

  公开号：EP2691393A1

  公开（公告）日：2014-02-05
• US8697673B2
  申请人：——

  公开号：US8697673B2

  公开（公告）日：2014-04-15
• US9067934B2
  申请人：——

  公开号：US9067934B2

  公开（公告）日：2015-06-30
• [EN] NOVEL BICYCLIC PYRIDINONES<br/>[FR] NOUVELLES PYRIDONES BICYCLIQUES
  申请人：PFIZER

  公开号：WO2012131539A1

  公开（公告）日：2012-10-04

  Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula (I) as defined herein. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.