3-cyclopropylmethoxy-4-methanesulfonylaminobenzoic acid methyl ester | 1239278-73-9

• 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: 3-cyclopropylmethoxy-4-methanesulfonylaminobenzoic acid methyl ester
• 英文别名: methyl 3-(cyclopropylmethoxy)-4-(methylsulfonamido)benzoate；3-Cyclopropylmethoxy-4-methanesulfonylamino-benzoic acid methyl ester；methyl 3-(cyclopropylmethoxy)-4-(methanesulfonamido)benzoate
• CAS: 1239278-73-9
• 化学式: C₁₃H₁₇NO₅S
• 分子量: 299.348
• InChiKey: GQMHONZRUQHECG-UHFFFAOYSA-N

物化性质

• 沸点：
  452.2±55.0 °C(Predicted)
• 密度：
  1.353±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  90.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-cyclopropylmethoxy-4-methanesulfonylaminobenzoic acid methyl ester 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 9.0h， 生成 (S)-4-(2-(4-(N-(tert-butoxycarbonyl)-methylsulfonamido)-3-(cyclopropylmethoxy)benzoyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 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：

  3-羟基-4-硝基苯甲酸甲酯 在 吡啶 、 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 potassium iodide 作用下， 以 甲醇 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 20.0~50.0 ℃ 、137.9 kPa 条件下， 反应 31.0h， 生成 3-cyclopropylmethoxy-4-methanesulfonylaminobenzoic acid methyl ester
  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：US20130079313A1

  公开（公告）日：2013-03-28

  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）的抑制剂。更具体地，该发明涉及1-苯基-2-吡啶基烷基醇衍生物，制备这类化合物的方法，含有它们的组合物以及它们的治疗用途。
• [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 PHOSPHODIESTÉRASE
  申请人：CHIESI FARMA SPA

  公开号：WO2013045280A1

  公开（公告）日：2013-04-04

  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）的抑制剂。更具体地，该发明涉及1-苯基-2-吡啶基烷基醇衍生物，制备这类化合物的方法，含有它们的组合物以及它们的治疗用途。
• PROCESS FOR THE PREPARATION OF A PDE4 INHIBITOR
  申请人：CHIESI FARMACEUTICI S.p.A.

  公开号：US20150111931A1

  公开（公告）日：2015-04-23

  The present invention relates to a process for the preparation of compounds endowed with phosphodiesterase (PDE4) inhibitory activity having formula (I). The invention also relates to the process for the isolation by crystallization of the compound (I) and to its use for the preparation of pharmaceutical compositions for inhalation in combination with suitable carriers or vehicles. The present invention also relates to solvates and crystal forms of a compound of formula (I). The synthesized product is suitable for use in pharmaceutical applications for instance in the treatment of respiratory diseases.

  本发明涉及一种制备具有磷酸二酯酶（PDE4）抑制活性的化合物（I）的方法。该发明还涉及通过结晶分离化合物（I）的方法，以及将其与适当载体或载体组合用于制备吸入用药物组合物的方法。本发明还涉及化合物（I）的溶剂合物和晶型。合成的产品适用于药用应用，例如用于治疗呼吸系统疾病。
• [EN] PROCESS FOR THE PREPARATION OF A PDE4 INHIBITOR<br/>[FR] PROCÉDÉ DE PRÉPARATION D'UN INHIBITEUR DE LA PDE4
  申请人：CHIESI FARMA SPA

  公开号：WO2015059050A1

  公开（公告）日：2015-04-30

  The present invention relates to a process and intermediates for the preparation of compounds endowed with phosphodiesterase (PDE4) inhibitory activity having formula (I). The invention also relates to the process for the isolation by crystallization of the compound (I) and to its use for the preparation of pharmaceutical compositions for inhalation in combination with suitable carriers or vehicles. The present invention also relates to solvates and crystal forms of a compound of formula (I). The synthesized product is suitable for use in pharmaceutical applications for instance in the treatment of respiratory diseases.

  本发明涉及一种用于制备具有磷酸二酯酶（PDE4）抑制活性的化合物的过程和中间体，其具有化学式(I)。该发明还涉及通过结晶分离化合物(I)的过程，以及将其与适当载体或溶剂结合用于制备用于吸入的药物组合物的用途。本发明还涉及化合物化学式(I)的溶剂合物和晶型。合成的产品适用于药物应用，例如用于治疗呼吸道疾病。
• 1-PHENYL-2-PYRIDINYL ALKYL ALCOHOL COMPOUNDS AS PHOSPHODIESTERASE INHIBITORS
  申请人：Amari Gabriele

  公开号：US20100204256A1

  公开（公告）日：2010-08-12

  1-Phenyl-2-pyridinyl alkyl alcohol compounds are effective as inhibitors of the phosphodiesterase 4 (PDE4) enzyme and may be used to prevent and/or treat certain diseases or conditions.

  苯基-吡啶基烷基醇化合物作为磷酸二酯酶4（PDE4）的抑制剂具有有效性，并可用于预防和/或治疗某些疾病或症状。