(RS)-2-(Cyclopropyl-{(2R)-2-hydroxy-3-[2-methyl-1-(naphthalen-2-yl)propan-2-ylamino]propoxy}methyl)benzoic acid | 1260380-25-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (RS)-2-(Cyclopropyl-{(2R)-2-hydroxy-3-[2-methyl-1-(naphthalen-2-yl)propan-2-ylamino]propoxy}methyl)benzoic acid
• 英文别名: 2-[cyclopropyl-[(2R)-2-hydroxy-3-[(2-methyl-1-naphthalen-2-ylpropan-2-yl)amino]propoxy]methyl]benzoic acid
• CAS: 1260380-25-3
• 化学式: C₂₈H₃₃NO₄
• 分子量: 447.574
• InChiKey: XANOFYBHZAZXBD-GEPVFLLWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  33
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  78.8
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-[cyclopropyl-[(2R)-2-hydroxy-3-[(2-methyl-1-naphthalen-2-ylpropan-2-yl)amino]propoxy]methyl]benzonitrile 在 potassium hydroxide 作用下， 以 乙二醇 为溶剂， 反应 8.0h， 生成 (RS)-2-(Cyclopropyl-{(2R)-2-hydroxy-3-[2-methyl-1-(naphthalen-2-yl)propan-2-ylamino]propoxy}methyl)benzoic 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