6-trifluoromethylsulfonyloxy-8-(3-nitrophenyl)-1,7-naphthyridine | 261960-44-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 6-trifluoromethylsulfonyloxy-8-(3-nitrophenyl)-1,7-naphthyridine
• 英文别名: [8-(3-nitrophenyl)-1,7-naphthyridin-6-yl] trifluoromethanesulfonate
• CAS: 261960-44-5
• 化学式: C₁₅H₈F₃N₃O₅S
• 分子量: 399.307
• InChiKey: ZHSRABCDAAITJX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  123
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  6-trifluoromethylsulfonyloxy-8-(3-nitrophenyl)-1,7-naphthyridine 在 三乙基硅烷 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以92%的产率得到8-(3-Nitro-phenyl)-[1,7]naphthyridine
  参考文献：
  名称：

  Palladium-Catalyzed Cross-Coupling Reactions for the Synthesis of 6,8-Disubstituted 1,7-Naphthyridines:  A Novel Class of Potent and Selective Phosphodiesterase Type 4D Inhibitors

  摘要：

  Recently, four subtypes of the human phosphodiesterase type 4 (PDE4A-D) enzyme have been described. So far, only very few PDE4 subtype-selective inhibitors are known. Herein; we describe the synthesis of 6,8-disubstituted 1,7-naphthyridines and their characterization as potent and selective inhibitors of PDE4D which suppress the oxidative burst in human eosinophils with IC50 values as low as 0.7 nM. SAR development and the extended use of palladium-catalyzed cross-coupling reactions led to compound 11 which inhibited human PDE4D T-Vith an IC50 value of 1 nM. Thus, compound II was 55, 175, and 1000 times more potent in inhibiting PDE4D over PDE4B, PDE4A, sind PDE4C. In a Brown Norway rat model of allergic asthma, compound 11 when given by the oral route (1 mg/kg) reduced by more than 50% the influx of eosinophils, T-cells, and neutrophils into bronchoalveolar lavage fluid (BALF) samples obtained from antigen-challenged animals. Thus, PDE4D-selective inhibitors of the 1.,7-naphthyridine class have the potential as an oral therapy for treating asthma.

  DOI：

  10.1021/jm991094u
• 作为产物：
  描述：

  3-(氰基甲基)吡啶-2-甲腈 在 氢溴酸 、 potassium carbonate 、 三苯基膦 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 、 sodium nitrite 作用下， 以 溶剂黄146 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 8.0h， 生成 6-trifluoromethylsulfonyloxy-8-(3-nitrophenyl)-1,7-naphthyridine
  参考文献：
  名称：

  Palladium-Catalyzed Cross-Coupling Reactions for the Synthesis of 6,8-Disubstituted 1,7-Naphthyridines:  A Novel Class of Potent and Selective Phosphodiesterase Type 4D Inhibitors

  摘要：

  Recently, four subtypes of the human phosphodiesterase type 4 (PDE4A-D) enzyme have been described. So far, only very few PDE4 subtype-selective inhibitors are known. Herein; we describe the synthesis of 6,8-disubstituted 1,7-naphthyridines and their characterization as potent and selective inhibitors of PDE4D which suppress the oxidative burst in human eosinophils with IC50 values as low as 0.7 nM. SAR development and the extended use of palladium-catalyzed cross-coupling reactions led to compound 11 which inhibited human PDE4D T-Vith an IC50 value of 1 nM. Thus, compound II was 55, 175, and 1000 times more potent in inhibiting PDE4D over PDE4B, PDE4A, sind PDE4C. In a Brown Norway rat model of allergic asthma, compound 11 when given by the oral route (1 mg/kg) reduced by more than 50% the influx of eosinophils, T-cells, and neutrophils into bronchoalveolar lavage fluid (BALF) samples obtained from antigen-challenged animals. Thus, PDE4D-selective inhibitors of the 1.,7-naphthyridine class have the potential as an oral therapy for treating asthma.

  DOI：

  10.1021/jm991094u

文献信息

• Naphthyridine derivatives
  申请人：Novartis AG

  公开号：US06136821A1

  公开（公告）日：2000-10-24

  Novel 8-aryl-1,7-naphthyridines, in free or salt form, are PDE IV inhibitors and are thus useful as pharmaceuticals, e.g. for asthma therapy. Preferred compounds include compounds of formulae (I and II) wherein the R groups are as defined. Pharmaceutical compositions comprising the compounds, processes for preparation of the compounds and novel intermediates for use in the processes are disclosed.

  新型的8-芳基-1,7-萘啶类化合物，无论是自由形式还是盐形式，均为PDE IV 抑制剂，因此可用作药物，例如用于治疗哮喘。首选化合物包括式(I和II)中R基的化合物。揭示了包括这些化合物的药物组合物、制备这些化合物的方法以及用于这些方法的新型中间体。
• NAPHTHYRIDINE DERIVATIVES
  申请人：Novartis AG

  公开号：EP0934320B1

  公开（公告）日：2003-04-02
• US6136821A
  申请人：——

  公开号：US6136821A

  公开（公告）日：2000-10-24
• Palladium-Catalyzed Cross-Coupling Reactions for the Synthesis of 6,8-Disubstituted 1,7-Naphthyridines:  A Novel Class of Potent and Selective Phosphodiesterase Type 4D Inhibitors
  作者：Rene Hersperger、Katharine Bray-French、Lazzaro Mazzoni、Thomas Müller

  DOI：10.1021/jm991094u

  日期：2000.2.1

  Recently, four subtypes of the human phosphodiesterase type 4 (PDE4A-D) enzyme have been described. So far, only very few PDE4 subtype-selective inhibitors are known. Herein; we describe the synthesis of 6,8-disubstituted 1,7-naphthyridines and their characterization as potent and selective inhibitors of PDE4D which suppress the oxidative burst in human eosinophils with IC50 values as low as 0.7 nM. SAR development and the extended use of palladium-catalyzed cross-coupling reactions led to compound 11 which inhibited human PDE4D T-Vith an IC50 value of 1 nM. Thus, compound II was 55, 175, and 1000 times more potent in inhibiting PDE4D over PDE4B, PDE4A, sind PDE4C. In a Brown Norway rat model of allergic asthma, compound 11 when given by the oral route (1 mg/kg) reduced by more than 50% the influx of eosinophils, T-cells, and neutrophils into bronchoalveolar lavage fluid (BALF) samples obtained from antigen-challenged animals. Thus, PDE4D-selective inhibitors of the 1.,7-naphthyridine class have the potential as an oral therapy for treating asthma.