(R)-7-(trifluoromethoxy)-2,2-dimethylchroman-4-amine (R)-2-hydroxy-2-phenylacetate | 1144501-63-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: (R)-7-(trifluoromethoxy)-2,2-dimethylchroman-4-amine (R)-2-hydroxy-2-phenylacetate
• CAS: 1144501-63-2
• 化学式: C₈H₈O₃*C₁₂H₁₄F₃NO₂
• 分子量: 413.394
• InChiKey: QMVKCXMBTDWFFJ-XPNWLKPYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.95
• 重原子数：
  29.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  102.01
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (2,5-dioxopyrrolidin-1-yl) N-isoquinolin-5-ylcarbamate 、 (R)-7-(trifluoromethoxy)-2,2-dimethylchroman-4-amine (R)-2-hydroxy-2-phenylacetate 在 N,N-二异丙基乙胺 作用下， 生成 (R)-1-(7-trifluoromethoxy-2,2-dimethylchroman-4-yl)-3-(isoquinolin-5-yl)urea
  参考文献：
  名称：

  Discovery of (R)-1-(7-Chloro-2,2-bis(fluoromethyl)chroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea (A-1165442): A Temperature-Neutral Transient Receptor Potential Vanilloid-1 (TRPV1) Antagonist with Analgesic Efficacy

  摘要：

  The synthesis and characterization of a series of selective, orally bioavailable 1-(chroman-4-yl)urea TRPV1 antagonists is described. Whereas first-generation antagonists that inhibit all modes of TRPV1 activation can elicit hyperthermia, the compounds disclosed herein do not elevate core body temperature in preclinical models and only partially block acid activation of TRPV1. Advancing the SAR of this series led to the eventual identification of (R)-1-(7-chloro-2,2-bis(fluoromethyl)chroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea (A-1165442, 52), an analogue that possesses excellent pharmacological selectivity, has a favorable pharmacokinetic profile, and demonstrates good efficacy against osteoarthritis pain in rodents.

  DOI：

  10.1021/jm500916t