(S)-1-tert-butyl 2-(5-formyl-2-methoxyphenyl) pyrrolidine-1,2-dicarboxylate | 1548871-56-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-1-tert-butyl 2-(5-formyl-2-methoxyphenyl) pyrrolidine-1,2-dicarboxylate
• 英文别名: 1-O-tert-butyl 2-O-(5-formyl-2-methoxyphenyl) (2S)-pyrrolidine-1,2-dicarboxylate
• CAS: 1548871-56-2
• 化学式: C₁₈H₂₃NO₆
• 分子量: 349.384
• InChiKey: KBIKNIIKMKRAFK-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.81
• 重原子数：
  25.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  82.14
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (S)-1-tert-butyl 2-(5-formyl-2-methoxyphenyl) pyrrolidine-1,2-dicarboxylate 在 盐酸 、 4-二甲氨基吡啶 、 sodium chlorite 、 氨基磺酸 、 碳酸氢钠 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)-phenyl)-2-(3-hydroxy-4-methoxybenzoyloxy)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：

  异香兰素 、 BOC-L-脯氨酸 在 4-二甲氨基吡啶 异丙醚 、 potassium carbonate 、 Sodium sulfate-III 作用下， 以 N,N-二甲基甲酰胺 、 potassium carbonate 为溶剂， 反应 2.5h， 以to afford 400 mg of desired product (yield=87%)的产率得到(S)-1-tert-butyl 2-(5-formyl-2-methoxyphenyl) pyrrolidine-1,2-dicarboxylate
  参考文献：
  名称：

  1-PHENYL-2-PYRIDINYL ALKYL ALCOHOL DERIVATIVES AS PHOSPHODIESTERASE INHIBITORS

  摘要：

  描述的式(I)化合物是磷酸二酯酶4（PDE4）酶的抑制剂，可用于预防和/或治疗过敏疾病状态或呼吸道疾病，其特征是呼吸道阻塞。

  公开号：

  US20140155391A1

文献信息

• 1-PHENYL-2-PYRIDINYL ALKYL ALCOHOL DERIVATIVES AS PHOSPHODIESTERASE INHIBITORS
  申请人：CHIESI FARMACEUTICI S.p.A.

  公开号：US20140155391A1

  公开（公告）日：2014-06-05

  Compounds of formula (I) described herein are inhibitors of the phosphodiesterase 4 (PDE4) enzyme and are useful for the prevention and/or treatment of an allergic disease state or a disease of the respiratory tract characterized by airway obstruction.

  本文描述的化合物（I）的公式是磷酸二酯酶4（PDE4）酶的抑制剂，可用于预防和/或治疗由气道阻塞特征的过敏病状态或呼吸道疾病。
• US9944612B2
  申请人：——

  公开号：US9944612B2

  公开（公告）日：2018-04-17
• [EN] 1-PHENYL-2-PYRIDINYL ALKYL ALCOHOL DERIVATIVES AS PHOSPHODIESTERASE INHIBITORS<br/>[FR] DÉRIVÉS D'ALCOOL 1-PHÉNYL-2-PYRIDINYL ALKYLIQUE EN TANT QU'INHIBITEURS DE PHOSPHODIESTÉRASE
  申请人：CHIESI FARMA SPA

  公开号：WO2014086865A1

  公开（公告）日：2014-06-12

  The present invention relates to inhibitors of the phosphodiesterase 4 (PDE4) enzyme. More particularly, the invention relates to 1-phenyl-2-pyridinyl alkyl alcohol derivatives, to processes for the preparation thereof, compositions comprising them, combinations and therapeutic uses thereof.
• 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.