methyl 4-(N-(tert-butoxycarbonyl)methylsulfonamido)-3-(cyclopropylmethoxy)benzoate | 1239278-74-0

• 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 4-(N-(tert-butoxycarbonyl)methylsulfonamido)-3-(cyclopropylmethoxy)benzoate
• 英文别名: methyl 3-(cyclopropylmethoxy)-4-[(2-methylpropan-2-yl)oxycarbonyl-methylsulfonylamino]benzoate
• CAS: 1239278-74-0
• 化学式: C₁₈H₂₅NO₇S
• 分子量: 399.465
• InChiKey: DRFUDVZHSRFWDX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  108
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 4-(N-(tert-butoxycarbonyl)methylsulfonamido)-3-(cyclopropylmethoxy)benzoate 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 8.0h， 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 、 4-二甲氨基吡啶 、 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 potassium iodide 作用下， 以 甲醇 、 二氯甲烷 、 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 32.0h， 生成 methyl 4-(N-(tert-butoxycarbonyl)methylsulfonamido)-3-(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

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。
• 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。
• Benzoic acid (1-phenyl-2-pyridin-4-yl)ethyl esters as phosphodiesterase inhibitors
  申请人：CHIESI FARMACEUTICI S.p.A.

  公开号：EP2216327A1

  公开（公告）日：2010-08-11

  The present invention relates to inhibitors of the phosphodiesterase 4 (PDE4) enzyme. More particularly, the invention relates to compounds that are derivatives of -pheny1-2-pyridinyI alkyl alcohols, methods of preparing such compounds, compositions comprising them, combinations and therapeutic uses thereof. wherein n is 0 or 1; R1 and R2 may be the same or different, and are selected from the group consisting of: - linear or branched C1-C6 alkyl; - OR3 wherein R3 is C1-C6 alkyl optionally substituted by one or more C3-C7 cycloalkyl groups; and - HNSO2R4 wherein R4 is C1-C4 alkyl optionally substituted with one or more halogen atoms or with a C1-C4 group, wherein at least one of R1 and R2 is HNSO2R4.

  本发明涉及磷酸二酯酶4（PDE4）酶的抑制剂。更具体地，本发明涉及衍生自-苯基-2-吡啶基烷基醇的化合物，制备这种化合物的方法，包含它们的组合物和治疗用途的组合物，其中n为0或1；R1和R2可以相同也可以不同，并选自以下组：-线性或支链C1-C6烷基；-OR3，其中R3是C1-C6烷基，可以选择性地被一个或多个C3-C7环烷基团取代；和-HNSO2R4，其中R4是C1-C4烷基，可以选择性地被一个或多个卤素原子或C1-C4基团取代，其中R1和R2中至少有一个是HNSO2R4。
• Derivatives of 1-phenyl-2-pyridinyl alkyl alcohols as phosphodiesterase inhibitors
  申请人：Chiesi Farmaceutici S.p.A.

  公开号：US09265768B2

  公开（公告）日：2016-02-23

  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.

  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-吡啶基烷基醇的衍生物化合物，制备这些化合物的方法，含有它们的组合物和其治疗用途。