| 1257231-40-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• CAS: 1257231-40-5
• 化学式: C₄H₆O₆*C₁₃H₁₈FNO
• 分子量: 373.378
• InChiKey: DZFFLWAOSKBXCZ-IMWLJMTPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.04
• 重原子数：
  26.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  150.31
• 氢给体数：
  5.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  phenyl N-(3-methylisoquinolin-5-yl)carbamate 、 在 N,N-二异丙基乙胺 作用下， 生成 (R)-1-(2,2-diethyl-8-fluorochroman-4-yl)-3-(3-methylisoquinolin-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
• 作为产物：
  描述：

  D-酒石酸 、 (4R)-4-azido-2,2-diethyl-8-fluoro-3,4-dihydrochromene 在 palladium on activated carbon 、 氢气 作用下， 以 甲醇 、 异丙醇 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  Efficient and general asymmetric syntheses of (R)-chroman-4-amine salts

  摘要：

  Starting from a variety of substituted chroman-4-ones, a highly enantioselective CBS reduction using in situ-generated B-H catalyst gave (S)-chroman-4-ols. Azide inversion and reduction gave crude (R)-chroman-4-amines, which could be purified without chromatography by isolation as the (R)-mandelic or D-tartaric acid salts with good yields and excellent ee. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2010.09.006