methyl 3-(N-(tert-butoxycarbonyl)methylsulfonamido)-5-(cyclopropylmethoxy)benzoate | 1548870-64-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 3-(N-(tert-butoxycarbonyl)methylsulfonamido)-5-(cyclopropylmethoxy)benzoate
• CAS: 1548870-64-9
• 化学式: C₁₈H₂₅NO₇S
• 分子量: 399.465
• InChiKey: UYGYVJICRPRBNS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.96
• 重原子数：
  27.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  99.21
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  methyl 3-(N-(tert-butoxycarbonyl)methylsulfonamido)-5-(cyclopropylmethoxy)benzoate 在 盐酸 、 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 31.0h， 生成 (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(cyclopropylmethoxy)-5-(methylsulfonamido)benzoyloxy)ethyl)pyridine 1-oxide
  参考文献：
  名称：

  Novel Class of Benzoic Acid Ester Derivatives as Potent PDE4 Inhibitors for Inhaled Administration in the Treatment of Respiratory Diseases

  摘要：

  The first steps in the selection process of a new anti-inflammatory drug for the inhaled treatment of asthma and chronic obstructive pulmonary disease are herein described. A series of novel ester derivatives of 1-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3,5-di-chloropyriclin-4-yl) ethanol have been synthesized and evaluated for inhibitory activity toward cAMP-specific phosphodiesterase-4 (PDE4). In particular, esters of variously substituted benzoic acids were extensively explored, and structural modification of the alcoholic and benzoic moieties were performed to maximize the inhibitory potency. Several compounds with high activity in cell-free and cell-based assays were obtained. Through the evaluation of opportune in vitro ADME properties, a potential candidate suitable for inhaled administration in respiratory diseases was identified and tested in an in vivo model of pulmonary inflammation, proving its efficacy.

  DOI：

  10.1021/jm401549m
• 作为产物：
  描述：

  methyl 3-amino-5-(cyclopropylmethoxy)benzoate 在 吡啶 、 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 methyl 3-(N-(tert-butoxycarbonyl)methylsulfonamido)-5-(cyclopropylmethoxy)benzoate
  参考文献：
  名称：

  Novel Class of Benzoic Acid Ester Derivatives as Potent PDE4 Inhibitors for Inhaled Administration in the Treatment of Respiratory Diseases

  摘要：

  The first steps in the selection process of a new anti-inflammatory drug for the inhaled treatment of asthma and chronic obstructive pulmonary disease are herein described. A series of novel ester derivatives of 1-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3,5-di-chloropyriclin-4-yl) ethanol have been synthesized and evaluated for inhibitory activity toward cAMP-specific phosphodiesterase-4 (PDE4). In particular, esters of variously substituted benzoic acids were extensively explored, and structural modification of the alcoholic and benzoic moieties were performed to maximize the inhibitory potency. Several compounds with high activity in cell-free and cell-based assays were obtained. Through the evaluation of opportune in vitro ADME properties, a potential candidate suitable for inhaled administration in respiratory diseases was identified and tested in an in vivo model of pulmonary inflammation, proving its efficacy.

  DOI：

  10.1021/jm401549m