1-(5-bromo-3-(2-methylpyridin-3-yloxy)pyridin-2-yl)-3-methylurea | 1442668-51-0

• 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-methylpyridin-3-yloxy)pyridin-2-yl)-3-methylurea
• CAS: 1442668-51-0
• 化学式: C₁₃H₁₃BrN₄O₂
• 分子量: 337.176
• InChiKey: AWHAXDGHIZXLJV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.09
• 重原子数：
  20.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 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-methylpyridin-3-yloxy)pyridin-2-yl)-3-methylurea 在 tris-(dibenzylideneacetone)dipalladium(0) 、 N,N-二异丙基乙胺 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 1-Methyl-3-[3-(2-methylpyridin-3-yl)oxy-5-(1-methylsulfonylpiperidin-4-yl)sulfanylpyridin-2-yl]urea
  参考文献：
  名称：

  Discovery of 2-Pyridylureas as Glucokinase Activators

  摘要：

  Glucokinase (GK) is the rate-limiting step for insulin release from the pancreas in response to high levels of glucose. Flux through GK also contributes to reducing hepatic glucose outpout. Since many individuals with type 2 diabetes appear to have an inadequacy or defect in one or both of these processes, identifying compounds that can allosterically activate GK may address this issue. Herein we report the identification and initial optimization of a novel series of glucokinase activators (GKAs). Optimization led to the identification of 33 as compound that displayed activity in an oral glucose tolerance test (OGTT) in normal and diabetic mice.

  DOI：

  10.1021/jm501204z
• 作为产物：
  描述：

  5-溴-2-氰基-3-硝基吡啶 在 吡啶 、 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 水 、 potassium carbonate 、 potassium hydroxide 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 1-(5-bromo-3-(2-methylpyridin-3-yloxy)pyridin-2-yl)-3-methylurea
  参考文献：
  名称：

  Discovery of 2-Pyridylureas as Glucokinase Activators

  摘要：

  Glucokinase (GK) is the rate-limiting step for insulin release from the pancreas in response to high levels of glucose. Flux through GK also contributes to reducing hepatic glucose outpout. Since many individuals with type 2 diabetes appear to have an inadequacy or defect in one or both of these processes, identifying compounds that can allosterically activate GK may address this issue. Herein we report the identification and initial optimization of a novel series of glucokinase activators (GKAs). Optimization led to the identification of 33 as compound that displayed activity in an oral glucose tolerance test (OGTT) in normal and diabetic mice.

  DOI：

  10.1021/jm501204z

文献信息

• [EN] UREA COMPOUNDS AS GKA ACTIVATORS<br/>[FR] COMPOSÉS D'URÉE EN TANT QU'ACTIVATEURS DE LA GKA
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2013086397A1

  公开（公告）日：2013-06-13

  The present invention relates to compounds, to pharmaceutical compositions comprising the compounds, to a process for making the compounds and to the use of the compounds in therapy. More particularly, it relates to certain glucokinase activators of Formulas 1 and 1a, useful in the treatment of diseases and disorders that would benefit from activation of glucokinase.

  本发明涉及化合物，包括含有该化合物的药物组合物，制备该化合物的方法以及在治疗中使用该化合物。更具体地，涉及到某些葡萄糖激酶激活剂的1和1a式，可用于治疗需要激活葡萄糖激酶的疾病和障碍。