(R)-2-((1r,4r)-4-(4-(4-(2-ethylphenylcarbamoyl)-2-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)phenyl)cyclohexyl)acetic acid | 1578241-56-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: (R)-2-((1r,4r)-4-(4-(4-(2-ethylphenylcarbamoyl)-2-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)phenyl)cyclohexyl)acetic acid
• CAS: 1578241-56-1
• 化学式: C₃₂H₃₆N₂O₄
• 分子量: 512.649
• InChiKey: PUQLADUSPHHAJY-CQOQZXRMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.48
• 重原子数：
  38.0
• 可旋转键数：
  6.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  78.87
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  2-硝基-5-溴苯酚 在 [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(ll) dichloride 、 lithium hydroxide monohydrate 、 偶氮二甲酸二异丙酯 、 dimethyl sulfide borane 、 铁粉 、 potassium carbonate 、 溶剂黄146 、 N,N-二异丙基乙胺 、 三苯基膦 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.83h， 生成 (R)-2-((1r,4r)-4-(4-(4-(2-ethylphenylcarbamoyl)-2-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)phenyl)cyclohexyl)acetic 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

文献信息

• Development of Novel Benzomorpholine Class of Diacylglycerol Acyltransferase I Inhibitors
  作者：Gang Zhou、Nicolas Zorn、Pauline Ting、Robert Aslanian、Mingxiang Lin、John Cook、Jean Lachowicz、Albert Lin、Michelle Smith、Joyce Hwa、Margaret van Heek、Scott Walker

  DOI：10.1021/ml400527n

  日期：2014.5.8

  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.