ethyl {trans-4-[2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclohexyl}acetate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl {trans-4-[2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclohexyl}acetate
• 英文别名: Ethyl 2-[4-[2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclohexyl]acetate
• 化学式: C₂₂H₃₂BFO₄
• 分子量: 390.303
• InChiKey: VPMICINXFMDROE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.35
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-氯-3,5-二甲基吡嗪-2-甲酰胺 、 ethyl {trans-4-[2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclohexyl}acetate 在 potassium dihydrogenphosphate 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 作用下， 以 乙二醇二甲醚 、 乙醇 、 水 为溶剂， 反应 0.5h， 以24%的产率得到ethyl {trans-4-[4-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-fluorophenyl]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
• 作为产物：
  描述：

  4-氧代环己烷乙酸乙酯 在 1,1'-双(二苯基膦)二茂铁 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 2,6-二叔丁基-4-甲基吡啶 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 palladium 10% on activated carbon 、 氢气 、 potassium acetate 、 potassium carbonate 、 三乙胺 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 38.33h， 生成 ethyl {trans-4-[2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-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.