3-((4-(4-methoxyphenethoxy)phenethyl)amino)benzoic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 3-((4-(4-methoxyphenethoxy)phenethyl)amino)benzoic acid
• 英文别名: 3-[2-[4-[2-(4-Methoxyphenyl)ethoxy]phenyl]ethylamino]benzoic acid；3-[2-[4-[2-(4-methoxyphenyl)ethoxy]phenyl]ethylamino]benzoic acid
• 化学式: C₂₄H₂₅NO₄
• 分子量: 391.467
• InChiKey: YTIWMOJOJRGGHO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  67.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  对甲氧基苯乙醇 在 三溴化磷 、 potassium carbonate 、 三乙胺 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 3-((4-(4-methoxyphenethoxy)phenethyl)amino)benzoic acid
  参考文献：
  名称：

  Evolution of a 4-Benzyloxy-benzylamino Chemotype to Provide Efficacious, Potent, and Isoform Selective PPARα Agonists as Leads for Retinal Disorders

  摘要：

  Peroxisome proliferator-activated receptor alpha (PPAR alpha) is expressed in retinal Muller cells, endothelial cells, and in retinal pigment epithelium; agonism of PPAR alpha with genetic or pharmacological tools ameliorates inflammation, vascular leakage, neurodegeneration, and neovascularization associated with retinal diseases in animal models. As such, PPAR alpha is a promising drug target for diabetic retinopathy and age-related macular degeneration. Herein, we report proof-of-concept in vivo efficacy in an streptozotocin-induced vascular leakage model (rat) and preliminary pharmacokinetic assessment of a first-generation lead 4a (A91). Additionally, we present the design, synthesis, and evaluation of second-generation analogues, which led to the discovery of 4u and related compounds that reach cellular potencies <50 nM and exhibit >2,700-fold selectivity for PPAR alpha over other PPAR isoforms. These studies identify a pipeline of candidates positioned for detailed PK/PD and pre-clinical evaluation.

  DOI：

  10.1021/acs.jmedchem.9b01189