4-(cyclopropylmethoxy)-3-nitrobenzoic acid | 1019619-62-5

• 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: 4-(cyclopropylmethoxy)-3-nitrobenzoic acid
• CAS: 1019619-62-5
• 化学式: C₁₁H₁₁NO₅
• mdl: MFCD11136668
• 分子量: 237.212
• InChiKey: WOMZABZTHSHIAL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.363
• 拓扑面积：
  92.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(cyclopropylmethoxy)-3-nitrobenzoic acid 在 4-二甲氨基吡啶 、 tin(II) chloride dihdyrate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 (S)-4-(2-(3-amino-4-(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-硝基-4-羟基苯甲酸甲酯 在 水 、 potassium carbonate 、 sodium iodide 、 lithium hydroxide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 4-(cyclopropylmethoxy)-3-nitrobenzoic acid
  参考文献：
  名称：

  双靶点机制抗SARS-CoV-2联芳酰胺衍生物的设计、合成及生物学评价

  摘要：

  COVID-19 大流行凸显了开发有效小分子抗病毒药物的迫切需要。合成了 33 种新型联芳酰胺衍生物，并评估了其抗冠状病毒活性。一些重要的 SAR 被发现，并且深入的结构修饰产生了最活跃的化合物8b和8h 。 8h的广谱抗冠状病毒作用在RNA和蛋白质水平上得到了验证。 8h在多个阶段抑制冠状病毒复制，从病毒进入到病毒dsRNA 合成。作用机制表明8h可能同时作用于3CL pro和TMPRSS2而发挥抗冠状病毒作用。 8h与RdRp抑制剂联用对冠状病毒表现出协同抑制活性。该研究证实联芳酰胺衍生物可能是一类具有多靶点作用的新型潜在抗冠状病毒治疗药物，值得进一步研究。

  DOI：

  10.1016/j.ejmech.2023.115978

文献信息

• 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.
• Design, synthesis and biological evaluation of biaryl amide derivatives against SARS-CoV-2 with dual-target mechanism
  作者：Jiayu Li、Xiuli Zhong、Hongying Li、Zhihui Yu、Jianrui Li、Qionglu Duan、Yinghong Li、Fenbei Chen、Yanxiang Wang、Zhiyun Wu、Yonghua Liu、Zonggen Peng、Danqing Song

  DOI：10.1016/j.ejmech.2023.115978

  日期：2024.1

  mechanism of action showed that 8h may simultaneously act on 3CLpro and TMPRSS2 to display anti-coronaviral effects. 8h combined with RdRp inhibitor showed synergistic inhibitory activity against coronavirus. This study confirmed that biaryl amide derivatives may be a new class of potential therapeutic agents against coronavirus with multiple target effect, worthy of further investigation.

  COVID-19 大流行凸显了开发有效小分子抗病毒药物的迫切需要。合成了 33 种新型联芳酰胺衍生物，并评估了其抗冠状病毒活性。一些重要的 SAR 被发现，并且深入的结构修饰产生了最活跃的化合物8b和8h 。 8h的广谱抗冠状病毒作用在RNA和蛋白质水平上得到了验证。 8h在多个阶段抑制冠状病毒复制，从病毒进入到病毒dsRNA 合成。作用机制表明8h可能同时作用于3CL pro和TMPRSS2而发挥抗冠状病毒作用。 8h与RdRp抑制剂联用对冠状病毒表现出协同抑制活性。该研究证实联芳酰胺衍生物可能是一类具有多靶点作用的新型潜在抗冠状病毒治疗药物，值得进一步研究。