ethyl 2'-(1-((R)-2-hydroxy-3-((2-methyl-1-(naphthalen-2-yl)propan-2-yl)amino)propoxy)ethyl)-[1,1'-biphenyl]-4-carboxylate | 1260380-42-4

• 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: ethyl 2'-(1-((R)-2-hydroxy-3-((2-methyl-1-(naphthalen-2-yl)propan-2-yl)amino)propoxy)ethyl)-[1,1'-biphenyl]-4-carboxylate
• CAS: 1260380-42-4
• 化学式: C₃₄H₃₉NO₄
• 分子量: 525.688
• InChiKey: QKKDSXMJAXJBOH-BXFARTRRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.73
• 重原子数：
  39.0
• 可旋转键数：
  12.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  67.79
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  ethyl 2'-(1-((R)-2-hydroxy-3-((2-methyl-1-(naphthalen-2-yl)propan-2-yl)amino)propoxy)ethyl)-[1,1'-biphenyl]-4-carboxylate 在 水 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 2'-[1-[(2R)-2-hydroxy-3-[[2-methyl-1-(naphthalen-2-yl)propan-2-yl]amino]propoxy]ethyl]biphenyl-4-carboxylic acid
  参考文献：
  名称：

  Discovery of a Potent and Short−Acting Oral Calcilytic with a Pulsatile Secretion of Parathyroid Hormone

  摘要：

  Short-acting oral calcilytics, calcium-sensing receptor (CaSR) antagonists, have been considered as alternatives for parathyroid hormone (PTH), an injectable bone anabolic drug used in the treatment of osteoporosis. Previously, we identified aminopropandiol 1, which transiently stimulated endogenous PT H secretion in rats. However, the inhibition of cytochrome P450 (GYP) 2D6 and the low bioavailability of 1 remain to be solved. Attempts to change the physicochemical properties of the highly lipophilic amine 1 by introduction of a carboxylic acid group as well as further structural modifications led to the discovery of the highly potent biphenylcarboxylic acid 15, with a markedly reduced CYP2D6 inhibition and a significantly improved bioavailability. Compound 15 evoked a rapid and transient elevation of endogenous PTH levels in rats after oral administration in a dose-dependent manner at a dose as low as 1 mg/kg. The PTH secretion pattern correlated with the pharmacokinetic profile and agreed well with that of the exogenous PTH injection which exerts a bone anabolic effect.

  DOI：

  10.1021/ml100268k
• 作为产物：
  描述：

  1-(2-溴苯基)乙醇 在 potassium cyanide 、 manganese(IV) oxide 、 四(三苯基膦)钯 、 lithium perchlorate 、 sodium hydride 、 sodium carbonate 作用下， 以 乙醇 、 甲苯 为溶剂， 生成 ethyl 2'-(1-((R)-2-hydroxy-3-((2-methyl-1-(naphthalen-2-yl)propan-2-yl)amino)propoxy)ethyl)-[1,1'-biphenyl]-4-carboxylate
  参考文献：
  名称：

  Discovery of a Potent and Short−Acting Oral Calcilytic with a Pulsatile Secretion of Parathyroid Hormone

  摘要：

  Short-acting oral calcilytics, calcium-sensing receptor (CaSR) antagonists, have been considered as alternatives for parathyroid hormone (PTH), an injectable bone anabolic drug used in the treatment of osteoporosis. Previously, we identified aminopropandiol 1, which transiently stimulated endogenous PT H secretion in rats. However, the inhibition of cytochrome P450 (GYP) 2D6 and the low bioavailability of 1 remain to be solved. Attempts to change the physicochemical properties of the highly lipophilic amine 1 by introduction of a carboxylic acid group as well as further structural modifications led to the discovery of the highly potent biphenylcarboxylic acid 15, with a markedly reduced CYP2D6 inhibition and a significantly improved bioavailability. Compound 15 evoked a rapid and transient elevation of endogenous PTH levels in rats after oral administration in a dose-dependent manner at a dose as low as 1 mg/kg. The PTH secretion pattern correlated with the pharmacokinetic profile and agreed well with that of the exogenous PTH injection which exerts a bone anabolic effect.

  DOI：

  10.1021/ml100268k