4-[8-(3-Trifluoromethoxyphenyl)-[1,7]naphthyridin-6-yl]-cyclohexanecarboxylic acid ethyl ester | 524734-50-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-[8-(3-Trifluoromethoxyphenyl)-[1,7]naphthyridin-6-yl]-cyclohexanecarboxylic acid ethyl ester
• 英文别名: ethyl 4-[8-[3-(trifluoromethoxy)phenyl]-1,7-naphthyridin-6-yl]cyclohexane-1-carboxylate
• CAS: 524734-50-7
• 化学式: C₂₄H₂₃F₃N₂O₃
• 分子量: 444.453
• InChiKey: XXQUDVXNXOXFPV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  61.3
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-[8-(3-Trifluoromethoxyphenyl)-[1,7]naphthyridin-6-yl]-cyclohexanecarboxylic acid ethyl ester 在 水 、 lithium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 4-(8-(3-(trifluoromethoxy)phenyl)-1,7-naphthyridin-6-yl)-cyclohexanecarboxylic acid
  参考文献：
  名称：

  Solubility-Driven Optimization of Phosphodiesterase-4 Inhibitors Leading to a Clinical Candidate

  摘要：

  The solubility-driven optimization of a series of 1,7-napthyridine phosphodiesterase-4 inhibitors is described. Directed structural changes resulted in increased aqueous solubility, enabling superior pharmacokinetic properties with retention of PDE4 inhibition. A range of potent and orally bioavailable compounds with good in vivo efficacy in animal models of inflammation and reduced emetic potential compared to previously described drugs were synthesized. Compound 2d was taken forward as a clinical candidate for the treatment of COPD.

  DOI：

  10.1021/jm300459a
• 作为产物：
  描述：

  3-吡啶乙腈 在 三甲基氯硅烷 、 氢溴酸 、 双氧水 、 溶剂黄146 、 1,2-二溴乙烷 、 二甲氨基甲酰氯 、 锌 、 sodium nitrite 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 6.0h， 生成 4-[8-(3-Trifluoromethoxyphenyl)-[1,7]naphthyridin-6-yl]-cyclohexanecarboxylic acid ethyl ester
  参考文献：
  名称：

  Solubility-Driven Optimization of Phosphodiesterase-4 Inhibitors Leading to a Clinical Candidate

  摘要：

  The solubility-driven optimization of a series of 1,7-napthyridine phosphodiesterase-4 inhibitors is described. Directed structural changes resulted in increased aqueous solubility, enabling superior pharmacokinetic properties with retention of PDE4 inhibition. A range of potent and orally bioavailable compounds with good in vivo efficacy in animal models of inflammation and reduced emetic potential compared to previously described drugs were synthesized. Compound 2d was taken forward as a clinical candidate for the treatment of COPD.

  DOI：

  10.1021/jm300459a

文献信息

• Naphthyridine derivatives, their preparation and their use as phosphodiesterase isoenzyme 4 (pde4) inhibitors
  申请人：——

  公开号：US20040254212A1

  公开（公告）日：2004-12-16

  The invention relates to compounds of formula I 1 in free or salt form, where R 1 is a monovalent aromatic group having up to 10 carbon atoms, and R 2 is a cycloaliphatic group having up to 8 ring carbon atoms. Compositions containing them, methods for their preparation and their use as pharmaceuticals are also described.

  该发明涉及公式I1的化合物，以自由或盐形式存在，其中R1是具有最多10个碳原子的单价芳香基团，而R2是具有最多8个环碳原子的环烷基团。还描述了包含它们的组合物，它们的制备方法以及它们作为药物的用途。
• Naphthyridine derivatives, their preparation and their use as phosphodiesterase isoenzyme 4 (PDE4) inhibitors
  申请人：Novartis AG

  公开号：US07273875B2

  公开（公告）日：2007-09-25

  The invention relates to compounds of formula I in free or salt form, where R1 is a monovalent aromatic group having up to 10 carbon atoms, and R2 is a cycloaliphatic group having up to 8 ring carbon atoms. Compositions containing them, methods for their preparation and their use as pharmaceuticals are also described.

  本发明涉及公式I的化合物，其以自由或盐形式存在，其中R1是具有最多10个碳原子的一价芳香基团，而R2是具有最多8个环状碳原子的环状脂肪族基团。还描述了含有它们的组合物，它们的制备方法以及它们作为药物的用途。
• NAPHTHYRIDINE DERIVATIVES, THEIR PREPARATION AND THEIR USE AS PHOSPHODIESTERASE ISOENZYME 4 (PDE4) INHIBITORS
  申请人：Novartis AG

  公开号：EP1443925B1

  公开（公告）日：2006-12-27
• US7273875B2
  申请人：——

  公开号：US7273875B2

  公开（公告）日：2007-09-25
• [EN] NAPHTYRIDINE DERIVATIVES, THEIR PREPARATION AND THEIR USE AS PHOSPHODIESTERASE ISOENZYME 4 (PDE4) INHIBITORS<br/>[FR] DERIVES DE NAPHTHYRIDINE, PREPARATION ET UTILISATION EN TANT QU'INHIBITEURS DE L'ISO-ENZYME PHOSPHODIESTERASE 4(PDE4)
  申请人：NOVARTIS AG

  公开号：WO2003039544A1

  公开（公告）日：2003-05-15

  The invention relates to compounds of formula (I), in free or salt form, where R1 is a monovalent aromatic group having up to 10 carbon atoms, and R2 is a cycloaliphatic group having up to 8 ring carbon atoms. Compositions containing them, methods for their preparation and their use as phosphodiesterase isoenzyme 4 (PDE4) inhibitors are also described.