1-[4-(2-cyclobutylmethylthio-ethyl)-phenoxy]-2,3-epoxy-propane | 63686-83-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-[4-(2-cyclobutylmethylthio-ethyl)-phenoxy]-2,3-epoxy-propane
• 英文别名: 2-[[4-[2-(cyclobutylmethylsulfanyl)ethyl]phenoxy]methyl]oxirane
• CAS: 63686-83-9
• 化学式: C₁₆H₂₂O₂S
• 分子量: 278.415
• InChiKey: AJPUELIJKUJCKU-UHFFFAOYSA-N

物化性质

• 沸点：
  425.1±25.0 °C(Predicted)
• 密度：
  1.140±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  19
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  47.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-[4-(2-cyclobutylmethylthio-ethyl)-phenoxy]-2,3-epoxy-propane 、 异丙胺 反应 48.0h， 生成 1-[4-(2-Cyclobutylmethylthio-ethyl)-phenoxy]-3-isopropylamino-propan-2-ol
  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：

  cyclobutylmethyl 4-methylbenzenesulfonate 在 氢氧化钾 、 sodium hydroxide 、 吡啶盐酸盐 作用下， 以 甲醇 、 水 为溶剂， 反应 15.0h， 生成 1-[4-(2-cyclobutylmethylthio-ethyl)-phenoxy]-2,3-epoxy-propane
  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

• Phenol ethers
  申请人：Synthelabo

  公开号：US04252984A1

  公开（公告）日：1981-02-24

  The invention provides phenol ethers of the formula: ##STR1## wherein R is branched C.sub.3-4 alkyl, C.sub.3-4 cycloalkyl, branched cyano(C.sub.3-4 alkyl), phenyl(C.sub.2-3 alkyl), halophenyl(C.sub.2-3 alkyl), (C.sub.1-4 alkoxy)phenyl(C.sub.2-4 alkyl), or (C.sub.1-4 acyl)amino(C.sub.1-4 alkyl), alk is C.sub.1-4 alkyl substituted by a 3 to 6 membered cycloalkyl group, X is --O--, --S-- or --SO.sub.2 --; and R.sub.1 is --C.sub.1-4 alkyl- or --C.sub.1-4 alkoxy-, in their racemic and optically active forms, and their addition salts with pharmaceutically acceptable acids. These compounds are useful in therapy as .beta.-adrenergic blocking agents. Intermediates are also provided.

  该发明提供了以下结构的酚醚化合物：##STR1## 其中R是支链C.sub.3-4烷基、C.sub.3-4环烷基、支链氰基(C.sub.3-4烷基)、苯基(C.sub.2-3烷基)、卤代苯基(C.sub.2-3烷基)、(C.sub.1-4烷氧基)苯基(C.sub.2-4烷基)、或(C.sub.1-4酰基)氨基(C.sub.1-4烷基)，alk是3到6环烷基取代的C.sub.1-4烷基，X是--O--、--S--或--SO.sub.2--；R.sub.1是--C.sub.1-4烷基-或--C.sub.1-4烷氧基-，它们以外消旋和光学活性形式存在，并且与药用酸形成的加合物。这些化合物在治疗中作为β-肾上腺素受体阻滞剂具有用途。同时提供了中间体。
• US4252984A
  申请人：——

  公开号：US4252984A

  公开（公告）日：1981-02-24
• US4311708A
  申请人：——

  公开号：US4311708A

  公开（公告）日：1982-01-19
• 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
  作者：Philippe M. Manoury、Jean L. Binet、Jean Rousseau、Francoise M. Lefevre-Borg、Icilio G. Cavero

  DOI：10.1021/jm00389a008

  日期：1987.6

  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.