(E)-3-(3-bromo-2-methoxyphenyl)acrylic acid | 1548942-23-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-3-(3-bromo-2-methoxyphenyl)acrylic acid
• 英文别名: 3-(3-Bromo-2-methoxyphenyl)prop-2-enoic acid；(E)-3-(3-bromo-2-methoxyphenyl)prop-2-enoic acid
• CAS: 1548942-23-9
• 化学式: C₁₀H₉BrO₃
• 分子量: 257.084
• InChiKey: UOFWWUYKZWAQGO-AATRIKPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-3-(3-bromo-2-methoxyphenyl)acrylic acid 在 copper(l) iodide 、 氯化亚砜 、 sodium azide 、 sodium hydride 、 caesium carbonate 作用下， 以 N,N-二甲基乙酰胺 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 mineral oil 为溶剂， 反应 165.0h， 生成 2-(3-chlorophenethyl)-5-methoxy-6-(4-methyl-1H-imidazol-1-yl)isoquinolin-1(2H)-one
  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：

  丙二酸 、 3-溴-2-甲氧基苯甲醛 在 哌啶 作用下， 以 吡啶 为溶剂， 反应 6.0h， 以50%的产率得到(E)-3-(3-bromo-2-methoxyphenyl)acrylic acid
  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