3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)pyridine 1-oxide | 1113061-15-6

• 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: 3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)pyridine 1-oxide
• 英文别名: 3-cyclopropylmethoxy-4-difluoromethoxy-benzoic acid 1-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)-2-(3,5-dichloro-1-oxy-pyridin-4-yl)-ethyl ester；3-cyclopropylmethoxy-4-difluoromethoxy-benzoic acid 1-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)-2-(3,5-dichloro-1-oxypyridin-4-yl)-ethyl ester；[1-[3-(Cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoate
• CAS: 1113061-15-6
• 化学式: C₃₀H₂₇Cl₂F₄NO₇
• 分子量: 660.446
• InChiKey: JTGRNMGEASTCHA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  44
• 可旋转键数：
  16
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  88.7
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)pyridine 1-oxide 在 Chiralcel OD column 作用下， 以11%的产率得到(R)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)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：

  4-(二氟甲氧基)-3-(环丙基甲氧基)苯甲醛 在 4-二甲氨基吡啶 、 potassium tert-butylate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 75.0h， 生成 3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)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

文献信息

• "Derivatives of 1-phenyl-2-pyridinyl alkyl alcohols as phosphodiesterase inhibitors"
  申请人：CHIESI FARMACEUTICI S.p.A.

  公开号：EP2022783A1

  公开（公告）日：2009-02-11

  The invention relates to inhibitors of the phosphodiesterase 4 (PDE4) enzyme. More particularly, the invention relates to compounds that are derivatives of 1-phenyl-2-pyridinyl alkyl alcohols, methods of preparing such compounds, compositions containing them and therapeutic use thereof.

  这项发明涉及磷酸二酯酶4（PDE4）酶的抑制剂。更具体地说，这项发明涉及1-苯基-2-吡啶基烷基醇衍生物化合物，制备这些化合物的方法，含有它们的组合物以及它们的治疗用途。
• DERIVATIVES OF 1-PHENYL-2-PYRIDINYL ALKYL ALCOHOLS AS PHOSPHODIESTERASE INHIBITORS
  申请人：Delcanale Maurizio

  公开号：US20090048220A1

  公开（公告）日：2009-02-19

  Derivatives of 1-phenyl-2-pyridinyl alkyl alcohols are useful as inhibitors of the phosphodiesterase 4 (PDE4) enzyme.

  1-苯基-2-吡啶基烷基醇的衍生物可用作磷酸二酯酶4（PDE4）酶的抑制剂。
• US7923565B2
  申请人：——

  公开号：US7923565B2

  公开（公告）日：2011-04-12
• US8203000B2
  申请人：——

  公开号：US8203000B2

  公开（公告）日：2012-06-19
• [EN] DERIVATIVES OF 1-PHENYL-2-PYRIDINYL ALKYL ALCOHOLS AS PHOSPHODIESTERASE INHIBITORS<br/>[FR] DÉRIVÉS D'ALCOOLS ALKYLIQUES DE 1-PHÉNYL-2-PYRIDINYLE EN TANT QU'INHIBITEURS DE LA PHOSPHODIESTÉRASE
  申请人：CHIESI FARMA SPA

  公开号：WO2009018909A2

  公开（公告）日：2009-02-12

  The invention relates to inhibitors of the phosphodiesterase 4 (PDE4) enzyme. More particularly, the invention relates to compounds that are derivatives of 1-phenyl-2-pyridinyl alkyl alcohols, methods of preparing such compounds, compositions containing them and therapeutic use thereof.