1-(5-bromo-3-((2-ethylpyridin-3-yl)oxy)pyridin-2-yl)-3-methylurea | 1442668-65-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(5-bromo-3-((2-ethylpyridin-3-yl)oxy)pyridin-2-yl)-3-methylurea
• 英文别名: 1-(5-bromo-3-(2-ethylpyridin-3-yloxy)pyridin-2-yl)-3-methylurea
• CAS: 1442668-65-6
• 化学式: C₁₄H₁₅BrN₄O₂
• 分子量: 351.203
• InChiKey: VDJQOAYHUSBQNU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.35
• 重原子数：
  21.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  76.14
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  1-(5-bromo-3-((2-ethylpyridin-3-yl)oxy)pyridin-2-yl)-3-methylurea 在 四(三苯基膦)钯 、 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 144.0h， 生成 1-(5-(2-ethoxyethyl)-3-((2-ethylpyridin-3-yl)oxy)pyridin-2-yl)-3-methylurea
  参考文献：
  名称：

  C5-Alkyl-2-methylurea-Substituted Pyridines as a New Class of Glucokinase Activators

  摘要：

  Glucokinase (GK) activators represent a class of type 2 diabetes therapeutics actively pursued due to the central role that GK plays in regulating glucose homeostasis. Herein we report a novel C5-alkyl-2-methylurea-substituted pyridine series of GK activators derived from our previously reported thiazolylamino pyridine series. Our efforts in optimizing potency, enzyme kinetic properties, and metabolic stability led to the identification of compound 26 (AM-9514). This analogue showed a favorable combination of in vitro potency, enzyme kinetic properties, acceptable pharmacokinetic profiles in preclinical species, and robust efficacy in a rodent PD model.

  DOI：

  10.1021/ml500341w
• 作为产物：
  描述：

  2-溴-3-羟基吡啶 在 吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 N-溴代丁二酰亚胺(NBS) 、 硫酸 、 palladium 10% on activated carbon 、 氢气 、 sodium methylate 、 sodium hydride 、 三乙胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 145.0 ℃ 、413.7 kPa 条件下， 反应 10.0h， 生成 1-(5-bromo-3-((2-ethylpyridin-3-yl)oxy)pyridin-2-yl)-3-methylurea
  参考文献：
  名称：

  C5-Alkyl-2-methylurea-Substituted Pyridines as a New Class of Glucokinase Activators

  摘要：

  Glucokinase (GK) activators represent a class of type 2 diabetes therapeutics actively pursued due to the central role that GK plays in regulating glucose homeostasis. Herein we report a novel C5-alkyl-2-methylurea-substituted pyridine series of GK activators derived from our previously reported thiazolylamino pyridine series. Our efforts in optimizing potency, enzyme kinetic properties, and metabolic stability led to the identification of compound 26 (AM-9514). This analogue showed a favorable combination of in vitro potency, enzyme kinetic properties, acceptable pharmacokinetic profiles in preclinical species, and robust efficacy in a rodent PD model.

  DOI：

  10.1021/ml500341w