tert-butyl 1-[2-hydroxy-3-(4-phenoxyphenoxy)propyl]-3-(3-methyl-1,2,4-oxadiazol-5-yl)-indole-5-carboxylate | 1138029-01-2

• 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: tert-butyl 1-[2-hydroxy-3-(4-phenoxyphenoxy)propyl]-3-(3-methyl-1,2,4-oxadiazol-5-yl)-indole-5-carboxylate
• CAS: 1138029-01-2
• 化学式: C₃₁H₃₁N₃O₆
• 分子量: 541.604
• InChiKey: MKPOBCBJNWYKPS-UHFFFAOYSA-N

物化性质

• 沸点：
  733.4±70.0 °C(predicted)
• 密度：
  1.25±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.19
• 重原子数：
  40.0
• 可旋转键数：
  9.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  108.84
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 1-[2-hydroxy-3-(4-phenoxyphenoxy)propyl]-3-(3-methyl-1,2,4-oxadiazol-5-yl)-indole-5-carboxylate 在 乙酸酐 、 二甲基亚砜 作用下， 反应 18.0h， 以25%的产率得到tert-butyl 3-(3-methyl-1,2,4-oxadiazol-5-yl)-1-[2-oxo-3-(4-phenoxyphenoxypropyl)]indole-5-carboxylate
  参考文献：
  名称：

  1-(5-Carboxyindol-1-yl)propan-2-one Inhibitors of Human Cytosolic Phospholipase A₂α: Effect of Substituents in Position 3 of the Indole Scaffold on Inhibitory Potency, Metabolic Stability, Solubility, and Bioavailability

  摘要：

  Indole-5-carboxylic acids with 3-aryloxy-2-oxopropyl residues in position I have been found to be potent inhibitors of human cytosolic phospholipase A(2)alpha (cPLA(2)alpha). In the course of structure-activity relationship studies, we investigated the effect of a substitution of indole 3 position with acyl, alkyl, and oxadiazole residues. The highest increase of inhibitory potency could be achieved by a 3-methyl-1,2, 4-oxadiazol-5-yl-moiety. Appropriate compound 40 revealed an IC50 of 0.0021 mu M against isolated cPLA(2)alpha. In a cellular assay applying human platelets 40 blocked cPLA(2)alpha. activity even with an IC50 of 0.0006 mu M. Metabolic stability and aqueous solubility of the target compounds were also determined. Furthermore, one selected compound was tested for peroral bioavailability in mice.

  DOI：

  10.1021/jm101094p
• 作为产物：
  描述：

  4-苯氧基苯酚 、 tert-butyl 3-(3-methyl-1,2,4-oxadiazol-5-yl)-1-oxiranylmethylindole-5-carboxylate 在 4-二甲氨基吡啶 作用下， 反应 1.0h， 以38%的产率得到tert-butyl 1-[2-hydroxy-3-(4-phenoxyphenoxy)propyl]-3-(3-methyl-1,2,4-oxadiazol-5-yl)-indole-5-carboxylate
  参考文献：
  名称：

  1-(5-Carboxyindol-1-yl)propan-2-one Inhibitors of Human Cytosolic Phospholipase A₂α: Effect of Substituents in Position 3 of the Indole Scaffold on Inhibitory Potency, Metabolic Stability, Solubility, and Bioavailability

  摘要：

  Indole-5-carboxylic acids with 3-aryloxy-2-oxopropyl residues in position I have been found to be potent inhibitors of human cytosolic phospholipase A(2)alpha (cPLA(2)alpha). In the course of structure-activity relationship studies, we investigated the effect of a substitution of indole 3 position with acyl, alkyl, and oxadiazole residues. The highest increase of inhibitory potency could be achieved by a 3-methyl-1,2, 4-oxadiazol-5-yl-moiety. Appropriate compound 40 revealed an IC50 of 0.0021 mu M against isolated cPLA(2)alpha. In a cellular assay applying human platelets 40 blocked cPLA(2)alpha. activity even with an IC50 of 0.0006 mu M. Metabolic stability and aqueous solubility of the target compounds were also determined. Furthermore, one selected compound was tested for peroral bioavailability in mice.

  DOI：

  10.1021/jm101094p