(+/-)-1-O-(4-cyanophenyl)-2-O-tetradecylglycerol | 945213-72-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (+/-)-1-O-(4-cyanophenyl)-2-O-tetradecylglycerol
• CAS: 945213-72-9
• 化学式: C₂₄H₃₉NO₃
• 分子量: 389.579
• InChiKey: CSDBNVBFSDJCKQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.02
• 重原子数：
  28.0
• 可旋转键数：
  18.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  62.48
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (+/-)-1-O-(4-cyanophenyl)-2-O-tetradecylglycerol 在 盐酸羟胺 、 sodium hydride 、 potassium carbonate 、 三乙胺 作用下， 以 乙醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 50.0h， 生成 3-[4-[3-(4-phenylbutoxy)-2-tetradecoxypropoxy]phenyl]-4H-1,2,4-oxadiazol-5-one
  参考文献：
  名称：

  Inhibition of Secreted Phospholipase A₂. 4-Glycerol Derivatives of 4,5-Dihydro-3-(4-tetradecyloxybenzyl)-1,2,4-4H-oxadiazol-5-one with Broad Activities

  摘要：

  Secreted phospholipases A(2) (sPLA(2)s) have been reported to play an important role in various inflammatory conditions and thus represent an attractive therapeutic target. Previous SAR studies from our laboratory have revealed certain important features of our recently discovered specific hGIIA sPLA(2) inhibitors, and we report here the synthesis and biological activities of glycerol-containing derivatives of our lead compound III (Figure 1). Efficient and selective synthesis methods have been developed to make glycerol trisubstituted by different groups on desired positions. In terms of biological activities, the best compounds (A3, A6, and A15) are more active than III (Figure 1), as potent as Me-Indoxam, an sPLA(2)s inhibitor of reference, against hGIIA, hGV, and hGX sPLA(2)s and at least 10 times less active toward the GIB enzymes in two in vitro assay systems. By synthesis of enantiopure (S)-A6, we demonstrated that no important improvement of the inhibitory potency could be achieved by this approach. Furthermore, the results show that the global lipophilicity is likely responsible for the anti-PLA(2) activity and two oxadiazolone moieties seem too big to be accommodated by the active site of the hGIIA enzyme.

  DOI：

  10.1021/jm060082n
• 作为产物：
  描述：

  rac-3-(4-cyanophenoxy)-propane-1,2-diol 在 盐酸 、 4-二甲氨基吡啶 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 62.0h， 生成 (+/-)-1-O-(4-cyanophenyl)-2-O-tetradecylglycerol
  参考文献：
  名称：

  Inhibition of Secreted Phospholipase A₂. 4-Glycerol Derivatives of 4,5-Dihydro-3-(4-tetradecyloxybenzyl)-1,2,4-4H-oxadiazol-5-one with Broad Activities

  摘要：

  Secreted phospholipases A(2) (sPLA(2)s) have been reported to play an important role in various inflammatory conditions and thus represent an attractive therapeutic target. Previous SAR studies from our laboratory have revealed certain important features of our recently discovered specific hGIIA sPLA(2) inhibitors, and we report here the synthesis and biological activities of glycerol-containing derivatives of our lead compound III (Figure 1). Efficient and selective synthesis methods have been developed to make glycerol trisubstituted by different groups on desired positions. In terms of biological activities, the best compounds (A3, A6, and A15) are more active than III (Figure 1), as potent as Me-Indoxam, an sPLA(2)s inhibitor of reference, against hGIIA, hGV, and hGX sPLA(2)s and at least 10 times less active toward the GIB enzymes in two in vitro assay systems. By synthesis of enantiopure (S)-A6, we demonstrated that no important improvement of the inhibitory potency could be achieved by this approach. Furthermore, the results show that the global lipophilicity is likely responsible for the anti-PLA(2) activity and two oxadiazolone moieties seem too big to be accommodated by the active site of the hGIIA enzyme.

  DOI：

  10.1021/jm060082n