1-[8-(3-Chlorophenyl)-1,7-naphthyridin-6-yl]piperidine-4-carboxylic acid | 713145-67-6

• 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: 1-[8-(3-Chlorophenyl)-1,7-naphthyridin-6-yl]piperidine-4-carboxylic acid
• CAS: 713145-67-6
• 化学式: C₂₀H₁₈ClN₃O₂
• 分子量: 367.835
• InChiKey: RXBMPEMJBXRGAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  66.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-吡啶乙腈 在 氢溴酸 、 双氧水 、 溶剂黄146 、 二甲氨基甲酰氯 、 sodium nitrite 作用下， 以 二甲基亚砜 、 甲苯 为溶剂， 反应 52.5h， 生成 1-[8-(3-Chlorophenyl)-1,7-naphthyridin-6-yl]piperidine-4-carboxylic 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

文献信息

• Solubility-Driven Optimization of Phosphodiesterase-4 Inhibitors Leading to a Clinical Candidate
  作者：Neil J. Press、Roger J. Taylor、Joseph D. Fullerton、Pamela Tranter、Clive McCarthy、Thomas H. Keller、Nicola Arnold、David Beer、Lyndon Brown、Robert Cheung、Julie Christie、Alastair Denholm、Sandra Haberthuer、Julia D. I. Hatto、Mark Keenan、Mark K. Mercer、Helen Oakman、Helene Sahri、Andrew R. Tuffnell、Morris Tweed、John W. Tyler、Trixie Wagner、John R. Fozard、Alexandre Trifilieff

  DOI：10.1021/jm300459a

  日期：2012.9.13

  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.