1-(3-(环丙基甲氧基)-4-(二氟甲氧基)苯基)-2-(3,5-二氯-1-吡啶-4-基)乙酮 | 1001909-97-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 1-(3-(环丙基甲氧基)-4-(二氟甲氧基)苯基)-2-(3,5-二氯-1-吡啶-4-基)乙酮
• 英文名称: 1-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3,5-dichloro-1-pyridin-4-yl)ethanone
• 英文别名: 1-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-2-(3,5-dichloro-pyridin-4-yl)ethanone；1-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)-2-(3,5-dichloro-pyridin-4-yl)-ethanone；1-[3-(Cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloropyridin-4-yl)ethanone
• CAS: 1001909-97-2
• 化学式: C₁₈H₁₅Cl₂F₂NO₃
• 分子量: 402.225
• InChiKey: DQMKQWBAJIDXCN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  48.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(3-(环丙基甲氧基)-4-(二氟甲氧基)苯基)-2-(3,5-二氯-1-吡啶-4-基)乙酮 在 甲醇 、 Oxone 、 sodium tetrahydroborate 作用下， 以 甲醇 、 水 为溶剂， 反应 54.5h， 生成 (R/S)-1-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3,5-dichloro-1-oxypyridin-4-yl)ethanol
  参考文献：
  名称：

  PROCESS FOR THE PREPARATION OF A PDE4 INHIBITOR

  摘要：

  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。

  公开号：

  US20150111931A1
• 作为产物：
  描述：

  3-环丙甲氧基-4-二氟甲氧基苯甲酸 在 potassium carbonate 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 N,N-二甲基乙酰胺 为溶剂， 反应 1.0h， 生成 1-(3-(环丙基甲氧基)-4-(二氟甲氧基)苯基)-2-(3,5-二氯-1-吡啶-4-基)乙酮
  参考文献：
  名称：

  [EN] PROCESS FOR THE PREPARATION OF A PDE4 INHIBITOR
  [FR] PROCÉDÉ DE PRÉPARATION D'UN INHIBITEUR DE LA PDE4

  摘要：

  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。

  公开号：

  WO2015059050A1

文献信息

• Derivatives of 1-phenyl-2-pyridynyl alkylene alcohols as phosphodiesterase inhibitors
  申请人：Amari Gabriele

  公开号：US20080015226A1

  公开（公告）日：2008-01-17

  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-pyridynyl alkylene alcohols, methods of preparing such compounds, compositions containing them and therapeutic use thereof.

  该发明涉及磷酸二酯酶4（PDE4）酶的抑制剂。更具体地，该发明涉及1-苯基-2-吡啶基烷基醇衍生物化合物，制备这种化合物的方法，含有它们的组合物以及它们的治疗用途。
• CRYSTAL FORM OF A PDE4 INHIBITOR
  申请人：Chiesi Farmaceutici S.p.a.

  公开号：EP3293176A1

  公开（公告）日：2018-03-14

  The present invention relates to a crystal form of a compound of formula (I) having phosphodiesterase (PDE4) inhibitory activity and to pharmaceutical compositions for inhalation containing said form in combination with suitable carriers or vehicles. Such products are suitable for use in pharmaceutical applications for instance in the treatment of respiratory diseases.

  本发明涉及具有磷酸二酯酶（PDE4）抑制活性的式(I)化合物的晶体形式，以及含有上述形式的晶体与适当载体或载体结合的吸入用药物组合物。 此类产品适用于医药应用，例如治疗呼吸系统疾病。
• PROCESS FOR THE PREPARATION OF A CRYSTAL FORM OF A PDE4 INHIBITOR
  申请人：Chiesi Farmaceutici S.p.A.

  公开号：EP3798209A1

  公开（公告）日：2021-03-31

  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.

  本发明涉及一种具有式（I）的具有磷酸二酯酶（PDE4）抑制活性的化合物的制备方法。本发明还涉及通过结晶分离化合物(I)的工艺及其与适当载体或载体结合用于制备吸入用药物组合物的用途。本发明还涉及式（I）化合物的溶解物和晶体形式。本发明合成的产品适用于医药应用，例如治疗呼吸系统疾病。
• Process for the preparation of a PDE4 inhibitor
  申请人：CHIESI FARMACEUTICI S.p.A.

  公开号：US10323003B2

  公开（公告）日：2019-06-18

  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.

  本发明涉及一种具有式（I）的具有磷酸二酯酶（PDE4）抑制活性的化合物的制备方法。本发明还涉及通过结晶分离化合物(I)的工艺及其与适当载体或载体结合用于制备吸入用药物组合物的用途。本发明还涉及式（I）化合物的溶解物和晶体形式。本发明合成的产品适用于医药应用，例如治疗呼吸系统疾病。
• Novel Class of Benzoic Acid Ester Derivatives as Potent PDE4 Inhibitors for Inhaled Administration in the Treatment of Respiratory Diseases
  作者：Elisabetta Armani、Gabriele Amari、Andrea Rizzi、Renato De Fanti、Eleonora Ghidini、Carmelida Capaldi、Laura Carzaniga、Paola Caruso、Matilde Guala、Ilaria Peretto、Elena La Porta、Pier T. Bolzoni、Fabrizio Facchinetti、Chiara Carnini、Nadia Moretto、Riccardo Patacchini、Franco Bassani、Valentina Cenacchi、Roberta Volta、Francesco Amadei、Silvia Capacchi、Maurizio Delcanale、Paola Puccini、Silvia Catinella、Maurizio Civelli、Gino Villetti

  DOI：10.1021/jm401549m

  日期：2014.2.13

  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.