ethyl 6-{4-[trans-4-(2-cyanoethylcarbamoyl)cyclohexyl]phenyl}-3,5-dimethylpyrazine-2-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: ethyl 6-{4-[trans-4-(2-cyanoethylcarbamoyl)cyclohexyl]phenyl}-3,5-dimethylpyrazine-2-carboxylate
• 英文别名: Ethyl 6-[4-[4-(2-cyanoethylcarbamoyl)cyclohexyl]phenyl]-3,5-dimethylpyrazine-2-carboxylate；ethyl 6-[4-[4-(2-cyanoethylcarbamoyl)cyclohexyl]phenyl]-3,5-dimethylpyrazine-2-carboxylate
• 化学式: C₂₅H₃₀N₄O₃
• 分子量: 434.538
• InChiKey: MIYUICKGPFRRPO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 6-{4-[trans-4-(2-cyanoethylcarbamoyl)cyclohexyl]phenyl}-3,5-dimethylpyrazine-2-carboxylate 在 叠氮基三甲基硅烷 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氯化铵 、 N,N-二异丙基乙胺 、 三苯基膦 、 lithium hydroxide 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 53.0h， 生成 3,5-dimethyl-6-{4-[trans-4-(1H-tetrazol-5-ylmethyl)-cyclohexyl]phenyl}pyrazine-2-carboxamide
  参考文献：
  名称：

  Design and Optimization of Pyrazinecarboxamide-Based Inhibitors of Diacylglycerol Acyltransferase 1 (DGAT1) Leading to a Clinical Candidate Dimethylpyrazinecarboxamide Phenylcyclohexylacetic Acid (AZD7687)

  摘要：

  A new series of pyrazinecarboxamide DGAT1 inhibitors was designed to address the need for a candidate drug with good potency, selectivity, and physical and DMPK properties combined with a low predicted dose in man. Rational design and optimization of this series led to the discovery of compound 30 (AZD7687), which met the project objectives for potency, selectivity, in particular over ACAT1, solubility, and preclinical PK profiles. This compound showed the anticipated excellent pharmacokinetic properties in human volunteers.

  DOI：

  10.1021/jm301296t
• 作为产物：
  描述：

  4-(4-羟基苯基)环己酮 在 吡啶 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium dihydrogenphosphate 、 palladium 10% on activated carbon 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氢气 、 sodium hydride 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙二醇二甲醚 、 乙醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 mineral oil 为溶剂， 140.0 ℃ 、500.01 kPa 条件下， 反应 34.0h， 生成 ethyl 6-{4-[trans-4-(2-cyanoethylcarbamoyl)cyclohexyl]phenyl}-3,5-dimethylpyrazine-2-carboxylate
  参考文献：
  名称：

  Design and Optimization of Pyrazinecarboxamide-Based Inhibitors of Diacylglycerol Acyltransferase 1 (DGAT1) Leading to a Clinical Candidate Dimethylpyrazinecarboxamide Phenylcyclohexylacetic Acid (AZD7687)

  摘要：

  A new series of pyrazinecarboxamide DGAT1 inhibitors was designed to address the need for a candidate drug with good potency, selectivity, and physical and DMPK properties combined with a low predicted dose in man. Rational design and optimization of this series led to the discovery of compound 30 (AZD7687), which met the project objectives for potency, selectivity, in particular over ACAT1, solubility, and preclinical PK profiles. This compound showed the anticipated excellent pharmacokinetic properties in human volunteers.

  DOI：

  10.1021/jm301296t