3-(4-(phenoxymethyl)phenyl)-1-(5-(trifluoromethyl)oxazol-2-yl)propan-1-ol | 1012330-54-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-(4-(phenoxymethyl)phenyl)-1-(5-(trifluoromethyl)oxazol-2-yl)propan-1-ol
• 英文别名: 3-[4-(Phenoxymethyl)phenyl]-1-[5-(trifluoromethyl)-1,3-oxazol-2-yl]propan-1-ol
• CAS: 1012330-54-9
• 化学式: C₂₀H₁₈F₃NO₃
• 分子量: 377.363
• InChiKey: PUDILPFXPAGIRK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  55.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-(4-(phenoxymethyl)phenyl)-1-(5-(trifluoromethyl)oxazol-2-yl)propan-1-ol 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以50%的产率得到3-[4-(Phenoxymethyl)phenyl]-1-[5-(trifluoromethyl)-1,3-oxazol-2-yl]propan-1-one
  参考文献：
  名称：

  Optimization of α-Ketooxazole Inhibitors of Fatty Acid Amide Hydrolase

  摘要：

  A series of alpha-ketooxazoles containing conformational constraints in the flexible C2 acyl side chain of 2 (OL-135) and representative oxazole C5 substituents were prepared and examined as inhibitors of fatty acid amide hydrolase (FAAH). Exceptionally potent and selective FAAH inhibitors emerged from the series (e.g., 6, K-i = 200 and 260 pM for rat and rhFAAH). With simple and small C5 oxazole substituents, each series bearing a biphenylethyl, phenoxyphenethyl, or (phenoxymethyl)phenethyl C2 side chain was found to follow a well-defined linear relationship between -log K-i and Hammett sigma(p) of a magnitude (rho = 2.7-3.0) that indicates that the substituent electronic effect dominates, confirming its fundamental importance to the series and further establishing its predictive value. Just as significantly, the nature of the C5 oxazole substituent substantially impacts the selectivity of the inhibitors whereas the effect of the C2 acyl chain was more subtle but still significant even in the small series examined. Combination of these independent features, which display generalized trends across a range of inhibitor series, simultaneously improves FAAH potency and selectivity and can provide exquisitely selective and potent FAAH inhibitors.

  DOI：

  10.1021/jm701210y
• 作为产物：
  描述：

  2-(1-(tert-butyldimethylsilyloxy)-3-(4-(phenoxymethyl)phenyl)propyl)-5-(trifluoromethyl)oxazole 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 以76%的产率得到3-(4-(phenoxymethyl)phenyl)-1-(5-(trifluoromethyl)oxazol-2-yl)propan-1-ol
  参考文献：
  名称：

  Optimization of α-Ketooxazole Inhibitors of Fatty Acid Amide Hydrolase

  摘要：

  A series of alpha-ketooxazoles containing conformational constraints in the flexible C2 acyl side chain of 2 (OL-135) and representative oxazole C5 substituents were prepared and examined as inhibitors of fatty acid amide hydrolase (FAAH). Exceptionally potent and selective FAAH inhibitors emerged from the series (e.g., 6, K-i = 200 and 260 pM for rat and rhFAAH). With simple and small C5 oxazole substituents, each series bearing a biphenylethyl, phenoxyphenethyl, or (phenoxymethyl)phenethyl C2 side chain was found to follow a well-defined linear relationship between -log K-i and Hammett sigma(p) of a magnitude (rho = 2.7-3.0) that indicates that the substituent electronic effect dominates, confirming its fundamental importance to the series and further establishing its predictive value. Just as significantly, the nature of the C5 oxazole substituent substantially impacts the selectivity of the inhibitors whereas the effect of the C2 acyl chain was more subtle but still significant even in the small series examined. Combination of these independent features, which display generalized trends across a range of inhibitor series, simultaneously improves FAAH potency and selectivity and can provide exquisitely selective and potent FAAH inhibitors.

  DOI：

  10.1021/jm701210y