(5R)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-3-[6-({2-[(phenylmethyl)oxy]ethyl}oxy)hexyl]-1,3-oxazolidin-2-one | 1228049-08-8

• 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)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-3-[6-({2-[(phenylmethyl)oxy]ethyl}oxy)hexyl]-1,3-oxazolidin-2-one
• 英文别名: (5R)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-3-[6-(2-phenylmethoxyethoxy)hexyl]-1,3-oxazolidin-2-one
• CAS: 1228049-08-8
• 化学式: C₂₈H₃₇NO₆
• 分子量: 483.605
• InChiKey: QKTGAKGZYWEYQP-SANMLTNESA-N

物化性质

• 沸点：
  654.5±55.0 °C(Predicted)
• 密度：
  1.136±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  35
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  66.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (5R)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-3-[6-({2-[(phenylmethyl)oxy]ethyl}oxy)hexyl]-1,3-oxazolidin-2-one 在 potassium trimethylsilonate 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 生成 (1R)-1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-{[6-({2-[(phenylmethyl)oxy]ethyl}oxy)hexyl]amino}ethanol
  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：

  维兰特罗杂质 、 (5R)-5-(2,2-二甲基-4H-1,3-苯并二氧杂环己-6-基)-1,3-恶唑烷-2-酮 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 1.5h， 以73%的产率得到(5R)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-3-[6-({2-[(phenylmethyl)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

文献信息

• Synthesis and Structure−Activity Relationships of Long-acting β₂ Adrenergic Receptor Agonists Incorporating Metabolic Inactivation: An Antedrug Approach
  作者：Panayiotis A. Procopiou、Victoria J. Barrett、Nicola J. Bevan、Keith Biggadike、Philip C. Box、Peter R. Butchers、Diane M. Coe、Richard Conroy、Amanda Emmons、Alison J. Ford、Duncan S. Holmes、Helen Horsley、Fern Kerr、Anne-Marie Li-Kwai-Cheung、Brian E. Looker、Inderjit S. Mann、Iain M. McLay、Valerie S. Morrison、Peter J. Mutch、Claire E. Smith、Paula Tomlin

  DOI：10.1021/jm100326d

  日期：2010.6.10

  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.