(5R)-3-[6-({4-[3-(cyclopentylsulfonyl)phenyl]butyl}oxy)-hexyl]-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one | 686351-01-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: (5R)-3-[6-({4-[3-(cyclopentylsulfonyl)phenyl]butyl}oxy)-hexyl]-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one
• 英文别名: (5R)-3-(6-{4-[3-(cyclopentylsulfonyl)phenyl]butoxy}hexyl)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one；(5R)-3-[6-[4-(3-cyclopentylsulfonylphenyl)butoxy]hexyl]-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one
• CAS: 686351-01-9
• 化学式: C₃₄H₄₇NO₇S
• 分子量: 613.816
• InChiKey: PYUXBFJOTIARFT-YTTGMZPUSA-N

物化性质

• 沸点：
  808.4±65.0 °C(Predicted)
• 密度：
  1.175±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  43
• 可旋转键数：
  15
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  99.8
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (5R)-3-[6-({4-[3-(cyclopentylsulfonyl)phenyl]butyl}oxy)-hexyl]-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one 在 potassium trimethylsilonate 、 溶剂黄146 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 3.0h， 生成 4-((1R)-2-{[6-({4-[3-(cyclopentylsulfonyl)phenyl]butyl}oxy)-hexyl]amino}-1-hydroxyethyl)-2-(hydroxymethyl)phenol
  参考文献：
  名称：

  Discovery of a Rapidly Metabolized, Long-Acting β₂ Adrenergic Receptor Agonist with a Short Onset Time Incorporating a Sulfone Group Suitable for Once-Daily Dosing

  摘要：

  A series of novel, potent, and selective human beta(2) adrenoceptor agonists incorporating a sulfone moiety on the terminal right-hand-side phenyl ring of (R)-salmeterol is presented. Sulfone 10b had salmeterol-like potency and selectivity profile, long duration of action on guinea pig trachea, and longer than salmeterol duration of action in vivo, suitable for once-daily dosing. It had lower than salmeterol oral absorption in rat, lower bioavailability in rat and dog, and a high turnover in human hepatocytes. It was metabolized in human hepatocytes by hydroxylation, oxidation, cleavage, and conjugation; most of the metabolites would be expected to have reduced or no beta(2) activity. The 4-biphenylsulfonic acid was identified as a crystalline, non-hygroscopic salt of 10b, suitable for inhaled delivery. Furthermore, it was free of any genetic toxicity issues and was considered as a backup to vilanterol.

  DOI：

  10.1021/jm401532g
• 作为产物：
  描述：

  (5R)-3-[6-(3-butyn-1-yloxy)-hexyl]-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one 在 platinum(IV) oxide 、 bis-triphenylphosphine-palladium(II) chloride 、 氢气 、 三乙胺 、 copper(l) chloride 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 3.5h， 生成 (5R)-3-[6-({4-[3-(cyclopentylsulfonyl)phenyl]butyl}oxy)-hexyl]-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one
  参考文献：
  名称：

  Discovery of a Rapidly Metabolized, Long-Acting β₂ Adrenergic Receptor Agonist with a Short Onset Time Incorporating a Sulfone Group Suitable for Once-Daily Dosing

  摘要：

  A series of novel, potent, and selective human beta(2) adrenoceptor agonists incorporating a sulfone moiety on the terminal right-hand-side phenyl ring of (R)-salmeterol is presented. Sulfone 10b had salmeterol-like potency and selectivity profile, long duration of action on guinea pig trachea, and longer than salmeterol duration of action in vivo, suitable for once-daily dosing. It had lower than salmeterol oral absorption in rat, lower bioavailability in rat and dog, and a high turnover in human hepatocytes. It was metabolized in human hepatocytes by hydroxylation, oxidation, cleavage, and conjugation; most of the metabolites would be expected to have reduced or no beta(2) activity. The 4-biphenylsulfonic acid was identified as a crystalline, non-hygroscopic salt of 10b, suitable for inhaled delivery. Furthermore, it was free of any genetic toxicity issues and was considered as a backup to vilanterol.

  DOI：

  10.1021/jm401532g

文献信息

• [EN] PHENETHANOLAMINE DERIVATIVE FOR THE TREATMENT OF RESPIRATORY DISEASES<br/>[FR] DERIVE DE PHENETHANOLAMINE UTILISE DANS LE TRAITEMENT DE MALADIES RESPIRATOIRES
  申请人：GLAXO GROUP LTD

  公开号：WO2004037773A1

  公开（公告）日：2004-05-06

  The present invention relates to novel compounds of formula (I), to a process for their manufacture, to pharmaceutical compositions containing them, and to their use in therapy, in particular their use in the prophylaxis and treatment of respiratory diseases.

  本发明涉及公式（I）的新化合物，以及其制备方法、含有它们的药物组合物，以及它们在治疗中的使用，特别是在预防和治疗呼吸道疾病中的使用。
• Phenethanolamine derivative for the treatment of respiratory diseases
  申请人：Chapman Michael Alan

  公开号：US20060205794A1

  公开（公告）日：2006-09-14

  The present invention relates to novel compounds of formula (I), to a process for their manufacture, to pharmaceutical compositions containing them, and to their use in therapy, in particular their use in the prophylaxis and treatment of respiratory diseases.

  本发明涉及公式（I）的新化合物，其制造方法，包含它们的药物组合物，以及它们在疗法中的应用，特别是它们在呼吸道疾病的预防和治疗中的应用。
• PHENETHANOLAMINE DERIVATIVE FOR THE TREATMENT OF RESPIRATORY DISEASES
  申请人：GLAXO GROUP LIMITED

  公开号：EP1556342B1

  公开（公告）日：2008-03-26
• US7442839B2
  申请人：——

  公开号：US7442839B2

  公开（公告）日：2008-10-28
• Discovery of a Rapidly Metabolized, Long-Acting β₂ Adrenergic Receptor Agonist with a Short Onset Time Incorporating a Sulfone Group Suitable for Once-Daily Dosing
  作者：Panayiotis A. Procopiou、Victoria J. Barrett、Keith Biggadike、Peter R. Butchers、Andrew Craven、Alison J. Ford、Stephen B. Guntrip、Duncan S. Holmes、Sara C. Hughes、Anne E. Jones、Brian E. Looker、Peter J. Mutch、Mark Ruston、Deborah Needham、Claire E. Smith

  DOI：10.1021/jm401532g

  日期：2014.1.9

  A series of novel, potent, and selective human beta(2) adrenoceptor agonists incorporating a sulfone moiety on the terminal right-hand-side phenyl ring of (R)-salmeterol is presented. Sulfone 10b had salmeterol-like potency and selectivity profile, long duration of action on guinea pig trachea, and longer than salmeterol duration of action in vivo, suitable for once-daily dosing. It had lower than salmeterol oral absorption in rat, lower bioavailability in rat and dog, and a high turnover in human hepatocytes. It was metabolized in human hepatocytes by hydroxylation, oxidation, cleavage, and conjugation; most of the metabolites would be expected to have reduced or no beta(2) activity. The 4-biphenylsulfonic acid was identified as a crystalline, non-hygroscopic salt of 10b, suitable for inhaled delivery. Furthermore, it was free of any genetic toxicity issues and was considered as a backup to vilanterol.