[3-(4'-benzylthio-3-chlorobiphenyl-4-yl)-1-[(methoxymethoxy)methyl]-1-(dimethylphosphoryloxymethyl)propyl]carbamic acid tert-butyl ester | 1235548-65-8

• 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: [3-(4'-benzylthio-3-chlorobiphenyl-4-yl)-1-[(methoxymethoxy)methyl]-1-(dimethylphosphoryloxymethyl)propyl]carbamic acid tert-butyl ester
• CAS: 1235548-65-8
• 化学式: C₃₃H₄₃ClNO₈PS
• 分子量: 680.199
• InChiKey: RAORDDBEBWKJAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.53
• 重原子数：
  45.0
• 可旋转键数：
  17.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  101.55
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  [3-(4'-benzylthio-3-chlorobiphenyl-4-yl)-1-[(methoxymethoxy)methyl]-1-(dimethylphosphoryloxymethyl)propyl]carbamic acid tert-butyl ester 在 碘代三甲硅烷 作用下， 以 二氯甲烷 为溶剂， 以29%的产率得到2-amino-4-(4'-benzylthio-3-chlorobiphenyl-4-yl)-2-(phosphoryloxymethyl)butanol
  参考文献：
  名称：

  Removal of Sphingosine 1-Phosphate Receptor-3 (S1P₃) Agonism is Essential, But Inadequate to Obtain Immunomodulating 2-Aminopropane-1,3-diol S1P₁ Agonists with Reduced Effect on Heart Rate

  摘要：

  A series of 2-substituted 2-aminopropane-1,3-diols having a biphenyl moiety and their phosphate esters were synthesized to obtain sphingosine 1-phosphate receptor-1 (S1P(1)) receptor agonists with potent immunomodulatory activity accompanied by little or no effect on heart rate. Many of the synthesized compounds sufficiently decreased the number of peripheral blood lymphocytes. Some of the phosphates had potent agonism at S1P(1) but no agonism at S1P(3), which had been reported to be a receptor responsible for heart rate reduction. Although high S1P(1)/S1P(3) selectivity was considered to be favorable to reduce the effect on heart rate, almost all the phosphates showed a remarkable heart rate lowering effect in vivo. The results suggest that other factors in addition to S1P(3) agonism should be responsible for the heart rate reduction caused by S1P(1) agonists. Only 2-amino-2-[2-[2'-fluoro-4'-(4-methylphenylthio)biphenyl-4-yl]ethyl]propane-1,3-diol (6d) was identified as a desired S1P(1) receptor agonist having both the immunomodulatory activity and an attenuated effect on heart rate by a unique screening flow using in vivo evaluating systems primarily.

  DOI：

  10.1021/jm901776q
• 作为产物：
  描述：

  [3-(4'-benzylthio-3-chlorobiphenyl-4-yl)-1-hydroxymethyl-1-[(methoxymethoxy)methyl]propyl]carbamic acid tert-butyl ester 、 三甲氧基磷 在 四溴化碳 、 原乙酸三乙酯 作用下， 以 吡啶 、 二氯甲烷 为溶剂， 反应 3.0h， 以78%的产率得到[3-(4'-benzylthio-3-chlorobiphenyl-4-yl)-1-[(methoxymethoxy)methyl]-1-(dimethylphosphoryloxymethyl)propyl]carbamic acid tert-butyl ester
  参考文献：
  名称：

  Removal of Sphingosine 1-Phosphate Receptor-3 (S1P₃) Agonism is Essential, But Inadequate to Obtain Immunomodulating 2-Aminopropane-1,3-diol S1P₁ Agonists with Reduced Effect on Heart Rate

  摘要：

  A series of 2-substituted 2-aminopropane-1,3-diols having a biphenyl moiety and their phosphate esters were synthesized to obtain sphingosine 1-phosphate receptor-1 (S1P(1)) receptor agonists with potent immunomodulatory activity accompanied by little or no effect on heart rate. Many of the synthesized compounds sufficiently decreased the number of peripheral blood lymphocytes. Some of the phosphates had potent agonism at S1P(1) but no agonism at S1P(3), which had been reported to be a receptor responsible for heart rate reduction. Although high S1P(1)/S1P(3) selectivity was considered to be favorable to reduce the effect on heart rate, almost all the phosphates showed a remarkable heart rate lowering effect in vivo. The results suggest that other factors in addition to S1P(3) agonism should be responsible for the heart rate reduction caused by S1P(1) agonists. Only 2-amino-2-[2-[2'-fluoro-4'-(4-methylphenylthio)biphenyl-4-yl]ethyl]propane-1,3-diol (6d) was identified as a desired S1P(1) receptor agonist having both the immunomodulatory activity and an attenuated effect on heart rate by a unique screening flow using in vivo evaluating systems primarily.

  DOI：

  10.1021/jm901776q