3-{3-cyano-4-[((2R)-3-{[1,1-dimethyl-2-(2-naphthalenyl)ethyl]-amino}-2-hydroxypropyl)oxy]phenyl}propanoic acid hydrochloride | 1192845-63-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: 3-{3-cyano-4-[((2R)-3-{[1,1-dimethyl-2-(2-naphthalenyl)ethyl]-amino}-2-hydroxypropyl)oxy]phenyl}propanoic acid hydrochloride
• 英文别名: 3-[3-cyano-4-[(2R)-2-hydroxy-3-[(2-methyl-1-naphthalen-2-ylpropan-2-yl)amino]propoxy]phenyl]propanoic acid;hydrochloride
• CAS: 1192845-63-8
• 化学式: C₂₇H₃₀N₂O₄*ClH
• 分子量: 483.007
• InChiKey: ZKWHABIEZQCVIW-GJFSDDNBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  34
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  103
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-{3-cyano-4-[((2R)-3-{[1,1-dimethyl-2-(2-naphthalenyl)ethyl]-amino}-2-hydroxypropyl)oxy]phenyl}propanoic acid 在 盐酸 作用下， 以 乙醚 、 甲苯 、 乙腈 为溶剂， 以38.4%的产率得到3-{3-cyano-4-[((2R)-3-{[1,1-dimethyl-2-(2-naphthalenyl)ethyl]-amino}-2-hydroxypropyl)oxy]phenyl}propanoic acid hydrochloride
  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

文献信息

• 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.