(R)-(-)-3-<4-<2-(cyclopropylmethoxy)ethyl>phenoxy>-1,2-propanodiol | 108008-06-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (R)-(-)-3-<4-<2-(cyclopropylmethoxy)ethyl>phenoxy>-1,2-propanodiol
• 英文别名: (R)-(-)-3-{4-[2-(cyclopropylmethoxy)ethyl]phenoxy}-1,2-propanodiol；(2R)-3-[4-[2-(cyclopropylmethoxy)ethyl]phenoxy]propane-1,2-diol
• CAS: 108008-06-6
• 化学式: C₁₅H₂₂O₄
• 分子量: 266.337
• InChiKey: NHYGVOXLHYXKGF-CQSZACIVSA-N

物化性质

• 沸点：
  433.6±35.0 °C(Predicted)
• 密度：
  1.174±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  19
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  58.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-(-)-3-<4-<2-(cyclopropylmethoxy)ethyl>phenoxy>-1,2-propanodiol 在 吡啶 、 sodium 作用下， 以 甲醇 、 乙醚 为溶剂， 反应 113.0h， 生成 (+)-Betaxolol
  参考文献：
  名称：

  Synthesis of a series of compounds related to betaxolol, a new .beta.1-adrenoceptor antagonist with a pharmacological and pharmacokinetic profile optimized for the treatment of chronic cardiovascular diseases

  摘要：

  A series of para-substituted phenoxypropanolamines has been synthesized and tested for beta-adrenoceptor blocking activity. Some derivatives (8, 11, 12, 20, 21) exhibited greater in vitro potency than the reference drugs metoprolol and propranolol. This series, in contrast to propranolol but similar to metoprolol, possesses cardioselectivity. The 3-[p-[(cycloalkylmethoxy)ethyl]phenoxy]-1-substituted-amino-2-prop anol derivatives 8 (cyclopropylmethoxyethyl: betaxolol) and 11 (cyclobutylmethoxyethyl) produced antihypertensive effects in spontaneously hypertensive rats. Betaxolol (Kerlon, 8) was found to exhibit an appropriate preclinical pharmacological and human pharmacokinetic profile (elevated oral bioavailability and prolonged plasma half-life) for the treatment of chronic cardiovascular diseases such as hypertension and angina.

  DOI：

  10.1021/jm00389a008
• 作为产物：
  描述：

  2-(4-苯甲氧基苯基)乙醇 在 palladium on activated charcoal 盐酸 、 sodium hydroxide 、 水 、 氢气 、 sodium hydride 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 50.0~60.0 ℃ 、344.73 kPa 条件下， 反应 42.0h， 生成 (R)-(-)-3-<4-<2-(cyclopropylmethoxy)ethyl>phenoxy>-1,2-propanodiol
  参考文献：
  名称：

  Synthesis of a series of compounds related to betaxolol, a new .beta.1-adrenoceptor antagonist with a pharmacological and pharmacokinetic profile optimized for the treatment of chronic cardiovascular diseases

  摘要：

  A series of para-substituted phenoxypropanolamines has been synthesized and tested for beta-adrenoceptor blocking activity. Some derivatives (8, 11, 12, 20, 21) exhibited greater in vitro potency than the reference drugs metoprolol and propranolol. This series, in contrast to propranolol but similar to metoprolol, possesses cardioselectivity. The 3-[p-[(cycloalkylmethoxy)ethyl]phenoxy]-1-substituted-amino-2-prop anol derivatives 8 (cyclopropylmethoxyethyl: betaxolol) and 11 (cyclobutylmethoxyethyl) produced antihypertensive effects in spontaneously hypertensive rats. Betaxolol (Kerlon, 8) was found to exhibit an appropriate preclinical pharmacological and human pharmacokinetic profile (elevated oral bioavailability and prolonged plasma half-life) for the treatment of chronic cardiovascular diseases such as hypertension and angina.

  DOI：

  10.1021/jm00389a008

文献信息

• A convenient synthesis of the enantiomerically pure β-blocker (S)-betaxolol using hydrolytic kinetic resolution
  作者：Ramesh A. Joshi、Dinesh R. Garud、M. Muthukrishnan、Rohini R. Joshi、M.K. Gurjar

  DOI：10.1016/j.tetasy.2005.10.028

  日期：2005.11

  Enantiopure (S)-betaxolol was prepared in an extremely simple and practical way using hydrolytic kinetic resolution of a terminal epoxide by Jacobsen's catalyst. High enantiomeric purity (99% ee) has been achieved and the method is amenable to industrial scale-up. (c) 2005 Elsevier Ltd. All rights reserved.