ethyl 4-(5-((1-ethyl-1H-pyrazol-5-yl)oxy)-6-(3-methylureido)pyridin-3-yl)butanoate | 1442670-46-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl 4-(5-((1-ethyl-1H-pyrazol-5-yl)oxy)-6-(3-methylureido)pyridin-3-yl)butanoate
• 英文别名: ethyl 4-[5-(2-ethylpyrazol-3-yl)oxy-6-(methylcarbamoylamino)pyridin-3-yl]butanoate
• CAS: 1442670-46-3
• 化学式: C₁₈H₂₅N₅O₄
• 分子量: 375.428
• InChiKey: CHCLJZZJJFVRTP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.73
• 重原子数：
  27.0
• 可旋转键数：
  9.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  107.37
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  ethyl 4-(5-((1-ethyl-1H-pyrazol-5-yl)oxy)-6-(3-methylureido)pyridin-3-yl)butanoate 、 甲基锂 以 四氢呋喃 、 乙醚 为溶剂， 反应 1.0h， 以72.5%的产率得到1-(3-((1-ethyl-1H-pyrazol-5-yl)oxy)-5-(4-hydroxy-4-methylpentyl)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-ethyl-1H-pyrazol-3-one 在 2-双环己基膦-2',6'-二甲氧基联苯 、 硫酸 、 palladium diacetate 、 sodium hydride 、 [双(三氟乙酰氧基)碘]苯 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 5.08h， 生成 ethyl 4-(5-((1-ethyl-1H-pyrazol-5-yl)oxy)-6-(3-methylureido)pyridin-3-yl)butanoate
  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