diethyl (4-hydroxy-3,5-dimethylphenylsulfanylmethyl)phosphonate | 1085957-26-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: diethyl (4-hydroxy-3,5-dimethylphenylsulfanylmethyl)phosphonate
• 英文别名: 4-(Diethoxyphosphorylmethylsulfanyl)-2,6-dimethylphenol
• CAS: 1085957-26-1
• 化学式: C₁₃H₂₁O₄PS
• 分子量: 304.347
• InChiKey: URIIZRAIQFLJIE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  81.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  diethyl (4-hydroxy-3,5-dimethylphenylsulfanylmethyl)phosphonate 、 bis(3-isopropyl-4-methoxyphenyl)iodonium tetrafluoroborate 在 铜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以60%的产率得到diethyl [4-(4'-methoxy-3'-isopropylphenoxy)-3,5-dimethyl-phenylsulfanylmethyl]phosphonate
  参考文献：
  名称：

  Synthesis and Biological Evaluation of a Series of Liver-Selective Phosphonic Acid Thyroid Hormone Receptor Agonists and Their Prodrugs

  摘要：

  Phosphonic acid (PA) thyroid hormone receptor (TR) agonists were synthesized to exploit the poor distribution of PA-based drugs to extrahepatic tissues and thereby to improve the therapeutic index. Nine PAs showed excellent TR binding affinities (TR beta(1), K-i < 10 nM), and most of them demonstrated significant cholesterol lowering effects in a cholesterol-fed rat (CFR) model. Unlike the corresponding carboxylic acid analogue and T-3, PA 22c demonstrated liver-selective effects by inducing maximal mitochondrial glycerol-3-phosphate dehydrogenase activity in rat liver while having no effect in the heart. Because of the low oral bioavailability of PA 22c, a series of prodrugs was synthesized and screened for oral efficacy in the CFR assay. The liver-activated cyclic 1-(3-chlorophenyl)-1,3-propanyl prodrug (MB07811) showed potent lipid lowering activity in the CFR (ED50 0.4 mg/kg, po) and good oral bioavailability (40%, rat) and was selected for development for the treatment of hypercholesterolemia.

  DOI：

  10.1021/jm800824d
• 作为产物：
  描述：

  diethyl (3,5-dimethyl-4-triisopropylsilanyloxyphenylsulfanyl)methylphosphonate 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以85%的产率得到diethyl (4-hydroxy-3,5-dimethylphenylsulfanylmethyl)phosphonate
  参考文献：
  名称：

  Synthesis and Biological Evaluation of a Series of Liver-Selective Phosphonic Acid Thyroid Hormone Receptor Agonists and Their Prodrugs

  摘要：

  Phosphonic acid (PA) thyroid hormone receptor (TR) agonists were synthesized to exploit the poor distribution of PA-based drugs to extrahepatic tissues and thereby to improve the therapeutic index. Nine PAs showed excellent TR binding affinities (TR beta(1), K-i < 10 nM), and most of them demonstrated significant cholesterol lowering effects in a cholesterol-fed rat (CFR) model. Unlike the corresponding carboxylic acid analogue and T-3, PA 22c demonstrated liver-selective effects by inducing maximal mitochondrial glycerol-3-phosphate dehydrogenase activity in rat liver while having no effect in the heart. Because of the low oral bioavailability of PA 22c, a series of prodrugs was synthesized and screened for oral efficacy in the CFR assay. The liver-activated cyclic 1-(3-chlorophenyl)-1,3-propanyl prodrug (MB07811) showed potent lipid lowering activity in the CFR (ED50 0.4 mg/kg, po) and good oral bioavailability (40%, rat) and was selected for development for the treatment of hypercholesterolemia.

  DOI：

  10.1021/jm800824d