methyl 3-((5-(2-ethyl-4-(phenylcarbamoyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)pyridin-2-yl)oxy)-2,2-dimethylpropanoat | 1578241-69-6

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: methyl 3-((5-(2-ethyl-4-(phenylcarbamoyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)pyridin-2-yl)oxy)-2,2-dimethylpropanoat
• CAS: 1578241-69-6
• 化学式: C₂₈H₃₁N₃O₅
• 分子量: 489.571
• InChiKey: BYNLDBPFEBRWCF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.54
• 重原子数：
  36.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  89.99
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  methyl 3-((5-(2-ethyl-4-(phenylcarbamoyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)pyridin-2-yl)oxy)-2,2-dimethylpropanoat 在 lithium hydroxide monohydrate 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 12.5h， 以40 mg的产率得到3-(5-(2-ethyl-4-(phenylcarbamoyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)pyridin-2-yloxy)-2,2-dimethylpropanoic acid
  参考文献：
  名称：

  Development of Novel Benzomorpholine Class of Diacylglycerol Acyltransferase I Inhibitors

  摘要：

  Diacylglycerol acyltransferase 1 (DGAT1) presents itself as a potential therapeutic target for obesity and diabetes for its important role in triglyceride biosynthesis. Herein we report the rational design of a novel class of DGAT1 inhibitors featuring a benzomorpholine core (23n). SAR exploration yielded compounds with good potency and selectivity as well as reasonable physical and pharmacokinetic properties. This class of DGAT1 inhibitors was tested in rodent models to evaluate DGAT1 inhibition as a novel approach for the treatment of metabolic diseases. Compound 23n conferred weight loss and a reduction in liver triglycerides when dosed chronically in mice with diet-induced obesity and depleted serum triglycerides following a lipid challenge.

  DOI：

  10.1021/ml400527n
• 作为产物：
  描述：

  methyl 3-((5-bromopyridin-2-yl)oxy)-2,2-dimethylpropanoate 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(ll) dichloride 、 potassium acetate 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 21.75h， 生成 methyl 3-((5-(2-ethyl-4-(phenylcarbamoyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)pyridin-2-yl)oxy)-2,2-dimethylpropanoat
  参考文献：
  名称：

  Development of Novel Benzomorpholine Class of Diacylglycerol Acyltransferase I Inhibitors

  摘要：

  Diacylglycerol acyltransferase 1 (DGAT1) presents itself as a potential therapeutic target for obesity and diabetes for its important role in triglyceride biosynthesis. Herein we report the rational design of a novel class of DGAT1 inhibitors featuring a benzomorpholine core (23n). SAR exploration yielded compounds with good potency and selectivity as well as reasonable physical and pharmacokinetic properties. This class of DGAT1 inhibitors was tested in rodent models to evaluate DGAT1 inhibition as a novel approach for the treatment of metabolic diseases. Compound 23n conferred weight loss and a reduction in liver triglycerides when dosed chronically in mice with diet-induced obesity and depleted serum triglycerides following a lipid challenge.

  DOI：

  10.1021/ml400527n