2-({6-[(5R)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-oxo-1,3-oxazolidin-3-yl]hexyl}oxy)ethyl methanesulfonate | 503068-55-1

• 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: 2-({6-[(5R)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-oxo-1,3-oxazolidin-3-yl]hexyl}oxy)ethyl methanesulfonate
• 英文别名: 2-[6-[(5R)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-oxo-1,3-oxazolidin-3-yl]hexoxy]ethyl methanesulfonate
• CAS: 503068-55-1
• 化学式: C₂₂H₃₃NO₈S
• 分子量: 471.572
• InChiKey: AFSYADFOBYKOID-FQEVSTJZSA-N

物化性质

• 沸点：
  689.4±55.0 °C(Predicted)
• 密度：
  1.222±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  32
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  109
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-萘甲醇 、 2-({6-[(5R)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-oxo-1,3-oxazolidin-3-yl]hexyl}oxy)ethyl methanesulfonate 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.75h， 生成 (5R)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-3-[6-({2-[(2-naphthalenylmethyl)oxy]ethyl}oxy)hexyl]-1,3-oxazolidin-2-one
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Long-acting β₂ Adrenergic Receptor Agonists Incorporating Metabolic Inactivation: An Antedrug Approach

  摘要：

  A series of saligenin beta(2) adrenoceptor agonist antedrugs having high clearance were prepared by reacting a protected saligenin oxazolidinone with protected hydroxyethoxyalkoxyalkyl bromides, followed by removal of the hydroxy-protecting group, alkylation, and final deprotection. The compounds were screened for beta(2), beta(1), and beta(3) agonist activity in CHO cells. The onset and duration of action in vitro of selected compounds were assessed on isolated superfused guinea pig trachea. Compound 13f had high potency, selectivity, fast onset, and long duration of action in vitro and was found to have long duration in vivo, low oral bioavailability in the rat, and to be rapidly metabolized. Crystalline salts of 13f (vilanterol) were identified that had suitable properties for inhaled administration. A proposed binding mode for 13f to the beta(2)-receptor is presented.

  DOI：

  10.1021/jm100326d
• 作为产物：
  描述：

  (5R)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-3-{6-[(2-hydroxyethyl)oxy]hexyl}-1,3-oxazolidin-2-one 、 甲基磺酰氯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以91%的产率得到2-({6-[(5R)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-oxo-1,3-oxazolidin-3-yl]hexyl}oxy)ethyl methanesulfonate
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Long-acting β₂ Adrenergic Receptor Agonists Incorporating Metabolic Inactivation: An Antedrug Approach

  摘要：

  A series of saligenin beta(2) adrenoceptor agonist antedrugs having high clearance were prepared by reacting a protected saligenin oxazolidinone with protected hydroxyethoxyalkoxyalkyl bromides, followed by removal of the hydroxy-protecting group, alkylation, and final deprotection. The compounds were screened for beta(2), beta(1), and beta(3) agonist activity in CHO cells. The onset and duration of action in vitro of selected compounds were assessed on isolated superfused guinea pig trachea. Compound 13f had high potency, selectivity, fast onset, and long duration of action in vitro and was found to have long duration in vivo, low oral bioavailability in the rat, and to be rapidly metabolized. Crystalline salts of 13f (vilanterol) were identified that had suitable properties for inhaled administration. A proposed binding mode for 13f to the beta(2)-receptor is presented.

  DOI：

  10.1021/jm100326d

文献信息

• [EN] PHENETHANOLAMINE DERIVATIVES FOR TREATMENT OF RESPIRATORY DISEASES<br/>[FR] DERIVES DE PHENETHANOLAMINE DESTINES AU TRAITEMENT DE MALADIES RESPIRATOIRES
  申请人：GLAXO GROUP LTD

  公开号：WO2003024439A1

  公开（公告）日：2003-03-27

  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，以及制造它们的方法，包含它们的制药组合物，以及它们在治疗中的应用，特别是在预防和治疗呼吸系统疾病方面的应用。
• Phenethanolamine derivatives for treatment of respiratory diseases
  申请人：Box Charles Philip

  公开号：US20050075394A1

  公开（公告）日：2005-04-07

  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，其制造过程，含有它们的药物组合物以及它们在治疗中的应用，特别是在预防和治疗呼吸系统疾病方面的应用。
• Inhalation devices for delivering phenethanolamine derivatives for the treatment of respiratory diseases
  申请人：BOX Philip Charles

  公开号：US20090068273A1

  公开（公告）日：2009-03-12

  The invention provides inhalation devices comprising a compound which is 4-(1R)-2-[(6-2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyethyl}-2-(hydroxymethyl)phenol; or a salt or solvate thereof, inhalation devices comprising formulations and combinations of the compound or a salt or solvate thereof, and methods for the treatment or prophylaxis of a clinical condition in a mammal by employing the inhalation devices

  本发明提供了包含4-(1R)-2-[(6-2-[(2,6-二氯苯基)氧基]乙氧基}己基)氨基]-1-羟基乙基}-2-(羟甲基)苯酚化合物的吸入装置；或者该化合物的盐或溶剂的吸入装置；包含该化合物或其盐或溶剂的配方和组合的吸入装置；以及使用吸入装置治疗或预防哺乳动物中的临床状况的方法。
• Phenethanolamine Derivatives for Treatment of Respiratory Diseases
  申请人：Box Charles Philip

  公开号：US20080003290A1

  公开（公告）日：2008-01-03

  The present invention relates to novel compounds of formula (1), 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 disease.

  本发明涉及公式（1）的新化合物，其制造过程，包含它们的药物组合物以及它们在治疗中的应用，特别是它们在呼吸系统疾病的预防和治疗中的应用。
• Inhalation device comprising phenethanolamine derivatives for treatment of respiratory diseases
  申请人：Glaxo Group Limited

  公开号：EP2042168A1

  公开（公告）日：2009-04-01

  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.

  本发明涉及式 (I) 的新型化合物、 的生产工艺、含有它们的药物组合物，以及它们在治疗中的用途，尤其是在预防和治疗呼吸系统疾病中的用途。