(R)-2-[1-(2-Bromophenyl)ethoxymethyl]oxirane | 804555-53-1

• 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: (R)-2-[1-(2-Bromophenyl)ethoxymethyl]oxirane
• 英文别名: (2R)-2-[1-(2-bromophenyl)ethoxymethyl]oxirane
• CAS: 804555-53-1
• 化学式: C₁₁H₁₃BrO₂
• 分子量: 257.127
• InChiKey: KBIKJTBONRUSQS-GKAPJAKFSA-N

物化性质

• 沸点：
  314.2±22.0 °C(Predicted)
• 密度：
  1.409±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  21.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (R)-2-[1-(2-Bromophenyl)ethoxymethyl]oxirane 在 potassium cyanide 、 manganese(IV) oxide 、 四(三苯基膦)钯 、 lithium perchlorate 、 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
• 作为产物：
  描述：

  R-(-)-glycidyl 3-nitrobenzenesulfonate 、 1-(2-溴苯基)乙醇 在 sodium hydride 作用下， 生成 (R)-2-[1-(2-Bromophenyl)ethoxymethyl]oxirane
  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

• CaSR antagonist
  申请人：Shinagawa Yuko

  公开号：US20060135572A1

  公开（公告）日：2006-06-22

  The present invention provides a compound having a calcium-sensitive receptor antagonistic action, a pharmaceutical composition containing the compound, particularly a calcium receptor antagonist and a therapeutic drug for osteoporosis. A compound represented by the following formula (1), a pharmaceutically acceptable salt thereof or an optically active form thereof: wherein each symbol is as defined in the description.

  本发明提供一种具有钙敏感受体拮抗作用的化合物，包含该化合物的制药组合物，特别是钙受体拮抗剂和治疗骨质疏松症的治疗药物。化合物由以下公式（1）表示，其药学上可接受的盐或其光学活性形式：其中每个符号如描述中所定义。
• CaSR ANTAGONIST
  申请人：Japan Tobacco Inc.

  公开号：EP1630157A1

  公开（公告）日：2006-03-01

  The present invention provides a compound having a calcium-sensitive receptor antagonistic action, a pharmaceutical composition containing the compound, particularly a calcium receptor antagonist and a therapeutic drug for osteoporosis. A compound represented by the following formula (1), a pharmaceutically acceptable salt thereof or an optically active form thereof: wherein each symbol is as defined in the description.

  本发明提供了一种具有钙敏感受体拮抗作用的化合物，一种含有该化合物的药物组合物，特别是一种钙受体拮抗剂和一种骨质疏松症治疗药物。由下式（1）代表的化合物、其药学上可接受的盐或其光学活性形式： 其中各符号如描述中所定义。
• EP1630157
  申请人：——

  公开号：——

  公开（公告）日：——
• US7285572B2
  申请人：——

  公开号：US7285572B2

  公开（公告）日：2007-10-23
• 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.