2-[2-(7-fluoronaphthalen-1-yloxy)ethyl]-7-(4-methyl-1H-imidazol-1-yl)-3,4-dihydro-1H-pyrido[1,2-a]pyrazine-1,6(2H)-dione | 1402002-39-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-[2-(7-fluoronaphthalen-1-yloxy)ethyl]-7-(4-methyl-1H-imidazol-1-yl)-3,4-dihydro-1H-pyrido[1,2-a]pyrazine-1,6(2H)-dione
• 英文别名: 2-{2-[(7-fluoronaphthalen-1-yl)oxy]ethyl}-7-(4-methyl-1H-imidazol-1-yl)-3,4-dihydro-2H-pyrido[1,2-a]pyrazine-1,6-dione；2-[2-(7-Fluoronaphthalen-1-yl)oxyethyl]-7-(4-methylimidazol-1-yl)-3,4-dihydropyrido[1,2-a]pyrazine-1,6-dione
• CAS: 1402002-39-4
• 化学式: C₂₄H₂₁FN₄O₃
• 分子量: 432.454
• InChiKey: JKYPDGRYYKKADH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  67.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

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

  Design, Synthesis, and Pharmacological Evaluation of a Novel Series of Pyridopyrazine-1,6-dione γ-Secretase Modulators

  摘要：

  Herein we describe the design and synthesis of a novel series of gamma-secretase modulators (GSMs) that incorporates a pyridopiperazine-1,6-dione ring system. To align improved potency with favorable ADME and in vitro safety, we applied prospective physicochemical property-driven design coupled with parallel medicinal chemistry techniques to arrive at a novel series containing a conformationally restricted core. Lead compound 51 exhibited good in vitro potency and ADME, which translated into a favorable in vivo pharmacokinetic profile. Furthermore, robust reduction of brain A beta 42 was observed in guinea pig at 30 mg/kg dosed orally. Through chemical biology efforts involving the design and synthesis of a clickable photoreactive probe, we demonstrated specific labeling of the presenilin N-terminal fragment (PS1-NTF) within the gamma-secretase complex, thus gaining insight into the binding site of this series of GSMs.

  DOI：

  10.1021/jm401782h

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：EP2691393B1

  公开（公告）日：2016-09-14
• 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