ethyl 3-(3-cyano-4-{[(2R)-2-oxiranylmethyl]oxy}phenyl)propanoate | 246219-38-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: ethyl 3-(3-cyano-4-{[(2R)-2-oxiranylmethyl]oxy}phenyl)propanoate
• 英文别名: ethyl 3-[3-cyano-4-[[(2R)-oxiran-2-yl]methoxy]phenyl]propanoate
• CAS: 246219-38-5
• 化学式: C₁₅H₁₇NO₄
• 分子量: 275.304
• InChiKey: PVYMFFCINMCTRQ-CYBMUJFWSA-N

物化性质

• 沸点：
  432.3±30.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  71.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 3-(3-cyano-4-{[(2R)-2-oxiranylmethyl]oxy}phenyl)propanoate 、 2-甲基-1-(萘-2-基)丙胺 以 乙醇 为溶剂， 反应 20.0h， 以82%的产率得到ethyl 3-{3-cyano-4-[((2R)-3-{[1,1-dimethyl-2-(2-naphthalenyl)-ethyl]amino}-2-hydroxypropyl)oxy]phenyl}propanoate
  参考文献：
  名称：

  Antagonists of the Calcium Receptor. 2. Amino Alcohol-Based Parathyroid Hormone Secretagogues

  摘要：

  When administered as a single agent to rats the previously reported calcium receptor antagonist 3 elicited a sustained elevation of plasma PTH resulting in no increase in overall bone mineral density. The lack of a bone building effect for analogue 3 was attributed to the large volume of distribution (V-dss(rat) = 11 L/kg) producing a protracted plasma PTH profile. Incorporation of a carboxylic acid functionality into the amino alcohol template led to the identification of 12 with a lower volume of distribution (V-dss(12) = 1.18 L/kg) and a shorter half-life. The zwitterionic nature of antagonist 12 necessitated the utility of an ester prodrug approach to increase overall permeability. Antagonist 12 elicited a rapid and transient increase in circulating levels of PTH following oral dosing of the ester prodrug 11 in the dog. The magnitude and duration of the increases in plasma levels of PTH would be expected to stimulate new bone formation.

  DOI：

  10.1021/jm900563e
• 作为产物：
  描述：

  (R)-(+)-间硝基苯磺酸缩水甘油酯 、 在 (R)-(+)-间硝基苯磺酸缩水甘油酯 作用下， 以82.4的产率得到ethyl 3-(3-cyano-4-{[(2R)-2-oxiranylmethyl]oxy}phenyl)propanoate
  参考文献：
  名称：

  Calcilytic compounds

  摘要：

  本发明提供了新型的钙离子受体拮抗剂化合物以及使用它们的方法。

  公开号：

  US20030018203A1

文献信息

• Calcilytic compounds
  申请人：——

  公开号：US20030018203A1

  公开（公告）日：2003-01-23

  Novel calcilytic compounds and methods of using them are provided.

  本发明提供了新型的钙离子受体拮抗剂化合物以及使用它们的方法。
• Antagonists of the Calcium Receptor. 2. Amino Alcohol-Based Parathyroid Hormone Secretagogues
  作者：Robert W. Marquis、Amparo M. Lago、James F. Callahan、Attiq Rahman、Xiaoyang Dong、George B. Stroup、Sandra Hoffman、Maxine Gowen、Eric G. DelMar、Bradford C. Van Wagenen、Sarah Logan、Scott Shimizu、John Fox、Edward F. Nemeth、Theresa Roethke、Brian R. Smith、Keith W. Ward、Pradip Bhatnagar

  DOI：10.1021/jm900563e

  日期：2009.11.12

  When administered as a single agent to rats the previously reported calcium receptor antagonist 3 elicited a sustained elevation of plasma PTH resulting in no increase in overall bone mineral density. The lack of a bone building effect for analogue 3 was attributed to the large volume of distribution (V-dss(rat) = 11 L/kg) producing a protracted plasma PTH profile. Incorporation of a carboxylic acid functionality into the amino alcohol template led to the identification of 12 with a lower volume of distribution (V-dss(12) = 1.18 L/kg) and a shorter half-life. The zwitterionic nature of antagonist 12 necessitated the utility of an ester prodrug approach to increase overall permeability. Antagonist 12 elicited a rapid and transient increase in circulating levels of PTH following oral dosing of the ester prodrug 11 in the dog. The magnitude and duration of the increases in plasma levels of PTH would be expected to stimulate new bone formation.