{3-[2-(2-hydroxyethylamino)ethoxy]phenyl}[4-(pent-4-ynyloxy)-phenyl]methanone | 1402004-49-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: {3-[2-(2-hydroxyethylamino)ethoxy]phenyl}[4-(pent-4-ynyloxy)-phenyl]methanone
• 英文别名: [3-[2-(2-Hydroxyethylamino)ethoxy]phenyl]-(4-pent-4-ynoxyphenyl)methanone
• CAS: 1402004-49-2
• 化学式: C₂₂H₂₅NO₄
• 分子量: 367.445
• InChiKey: IOAJJGYHZFBNIC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  27
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  67.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(4-methyl-1H-imidazol-1-yl)-6-oxo-1,6-dihydropyridine-2-carboxylic acid hydrobromide 、 {3-[2-(2-hydroxyethylamino)ethoxy]phenyl}[4-(pent-4-ynyloxy)-phenyl]methanone 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 二氯甲烷 为溶剂， 反应 19.0h， 以63%的产率得到7-(4-methyl-1H-imidazol-1-yl)-2-(2-{3-[4-(pent-4-yn-1-yloxy)-benzoyl]phenoxy}ethyl)-3,4-dihydro-2H-pyrido[1,2-a]pyrazine-1,6-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
• 作为产物：
  描述：

  (3-hydroxyphenyl)[4-(pent-4-ynyloxy)phenyl]methanone 在 caesium carbonate 作用下， 以 乙腈 为溶剂， 反应 3.0h， 生成 {3-[2-(2-hydroxyethylamino)ethoxy]phenyl}[4-(pent-4-ynyloxy)-phenyl]methanone
  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