Methyl 3-[cyclopropyl(hydroxy)methyl]benzoate | 1260380-39-9

• 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: Methyl 3-[cyclopropyl(hydroxy)methyl]benzoate
• 英文别名: methyl 3-[cyclopropyl(hydroxy)methyl]benzoate
• CAS: 1260380-39-9
• 化学式: C₁₂H₁₄O₃
• 分子量: 206.241
• InChiKey: JTIQRNBCRYCUSR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Methyl 3-[cyclopropyl(hydroxy)methyl]benzoate 、 R-(-)-glycidyl 3-nitrobenzenesulfonate 在 sodium hydride 作用下， 生成
  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

文献信息

• Discovery of a Potent and Short−Acting Oral Calcilytic with a Pulsatile Secretion of Parathyroid Hormone
  作者：Yuko Shinagawa、Teruhiko Inoue、Takeo Katsushima、Toshihiro Kiguchi、Taku Ikenogami、Naoki Ogawa、Kenji Fukuda、Kazuyuki Hirata、Kazuhito Harada、Masaki Takagi、Takashi Nakagawa、Shuichi Kimura、Yushi Matsuo、Mariko Maekawa、Mikio Hayashi、Yuki Soejima、Mitsuru Takahashi、Masanori Shindo、Hiromasa Hashimoto

  DOI：10.1021/ml100268k

  日期：2011.3.10

  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.