tert-butyl {trans-4-[4-(6-carbamoyl-3-methylpyrazin-2-yl)phenyl]cyclohexyl}acetate

• 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: tert-butyl {trans-4-[4-(6-carbamoyl-3-methylpyrazin-2-yl)phenyl]cyclohexyl}acetate
• 英文别名: Tert-butyl 2-[4-[4-(6-carbamoyl-3-methylpyrazin-2-yl)phenyl]cyclohexyl]acetate
• 化学式: C₂₄H₃₁N₃O₃
• 分子量: 409.528
• InChiKey: AHOPRPGTPOQYPW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  95.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl {trans-4-[4-(6-carbamoyl-3-methylpyrazin-2-yl)phenyl]cyclohexyl}acetate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以53%的产率得到{trans-4-[4-(6-carbamoyl-3-methylpyrazin-2-yl)phenyl]cyclohexyl} acetic acid
  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：

  二甲氧基膦酰基乙酸叔丁酯 在 吡啶 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium dihydrogenphosphate 、 palladium 10% on activated carbon 、 氢气 、 sodium hydride 、 氯化铵 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 、 N,N-二异丙基乙胺 、 lithium hydroxide 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， 150.0 ℃ 、500.01 kPa 条件下， 反应 13.5h， 生成 tert-butyl {trans-4-[4-(6-carbamoyl-3-methylpyrazin-2-yl)phenyl]cyclohexyl}acetate
  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

文献信息

• Design and Optimization of Pyrazinecarboxamide-Based Inhibitors of Diacylglycerol Acyltransferase 1 (DGAT1) Leading to a Clinical Candidate Dimethylpyrazinecarboxamide Phenylcyclohexylacetic Acid (AZD7687)
  作者：Jonas G. Barlind、Udo A. Bauer、Alan M. Birch、Susan Birtles、Linda K. Buckett、Roger J. Butlin、Robert D. M. Davies、Jan W. Eriksson、Clare D. Hammond、Ragnar Hovland、Petra Johannesson、Magnus J. Johansson、Paul D. Kemmitt、Bo T. Lindmark、Pablo Morentin Gutierrez、Tobias A. Noeske、Andreas Nordin、Charles J. O’Donnell、Annika U. Petersson、Alma Redzic、Andrew V. Turnbull、Johanna Vinblad

  DOI：10.1021/jm301296t

  日期：2012.12.13

  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.