4-{2-[3,4-Bis(difluoromethoxy)phenyl]-2-[6-(benzylamino)pyridin-3-yl]ethyl}pyridine | 306759-92-2

• 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-{2-[3,4-Bis(difluoromethoxy)phenyl]-2-[6-(benzylamino)pyridin-3-yl]ethyl}pyridine
• 英文别名: 4-{2-[3,4-Bis(difluoromethoxy)phenyl]-2-[6-(benzylamino)3-pyridyl]ethyl}pyridine；N-benzyl-5-[1-[3,4-bis(difluoromethoxy)phenyl]-2-pyridin-4-ylethyl]pyridin-2-amine
• CAS: 306759-92-2
• 化学式: C₂₇H₂₃F₄N₃O₂
• 分子量: 497.492
• InChiKey: PNMRASWJOZOUNO-UHFFFAOYSA-N

物化性质

• 沸点：
  572.4±50.0 °C(Predicted)
• 密度：
  1.295±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  36
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  56.3
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4-{2-[3,4-Bis(difluoromethoxy)phenyl]-2-[6-(benzylamino)pyridin-3-yl]ethyl}pyridine 在 吡啶 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 生成 4-{2-[3,4-Bis(difluoromethoxy)phenyl]-2-[6-(benzylamino)3-pyridyl]ethyl}pyridine-N-oxide
  参考文献：
  名称：

  Substituted aminopyridines as potent and selective phosphodiesterase-4 inhibitors

  摘要：

  The synthesis and the biological evaluation of new potent phosphodiesterase type 4 (PDE4) inhibitors are presented. This new series was elaborated by replacement of the metabolically resistant phenyl hexafluorocarbinol of L-791,943 (1) by a substituted aminopyridine residue, The structure-activity relationship of N-substitution on 3 led to the identification of (-)-3n which exhibited a good PDE4 inhibitor activity (HWB-TNFalpha=0.12 muM) and an improved pharmacokinetic profile over L-791,943 (rat t(1/2) = 2 h). (-)-3n was well tolerated in ferret with an emetic threshold of 30 mg/kg (po) and was found to be active in the ovalbumin-induced bronchoconstriction model in guinea pig (54%, 0.1 mg/kg, ip) as well as the ascaris-induced bronchoconstriction model in sheep (64%/97%. early,,late, 0.5 mg/kg. iv). (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)01030-2
• 作为产物：
  描述：

  (+/-)-[3,4-bis(difluoromethoxy)phenyl]-(2-bromopyridin-5-yl)methanol 在 盐酸 、 六甲基磷酰三胺 、 lithium hydroxide 、 copper(l) iodide 、 氯化亚砜 、 双(三甲基硅烷基)氨基钾 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 生成 4-{2-[3,4-Bis(difluoromethoxy)phenyl]-2-[6-(benzylamino)pyridin-3-yl]ethyl}pyridine
  参考文献：
  名称：

  Substituted aminopyridines as potent and selective phosphodiesterase-4 inhibitors

  摘要：

  The synthesis and the biological evaluation of new potent phosphodiesterase type 4 (PDE4) inhibitors are presented. This new series was elaborated by replacement of the metabolically resistant phenyl hexafluorocarbinol of L-791,943 (1) by a substituted aminopyridine residue, The structure-activity relationship of N-substitution on 3 led to the identification of (-)-3n which exhibited a good PDE4 inhibitor activity (HWB-TNFalpha=0.12 muM) and an improved pharmacokinetic profile over L-791,943 (rat t(1/2) = 2 h). (-)-3n was well tolerated in ferret with an emetic threshold of 30 mg/kg (po) and was found to be active in the ovalbumin-induced bronchoconstriction model in guinea pig (54%, 0.1 mg/kg, ip) as well as the ascaris-induced bronchoconstriction model in sheep (64%/97%. early,,late, 0.5 mg/kg. iv). (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)01030-2

文献信息

• Heterosubstituted pyridine derivatives as PDE4 inhibitors
  申请人：Merck Frosst Canada & Co.

  公开号：US06200993B1

  公开（公告）日：2001-03-13

  The invention encompasses the novel compound of Formula I useful in the treatment of diseases, including asthma, by raising the level of cyclic adenosine-3′,5′-monophosphate (cAMP) through the inhibition of phosphodiesterase IV (PDE 4). or a pharmaceutically acceptable salt or hydrate thereof. The invention also encompasses pharmaceutical compositions and methods for treatment.

  本发明涵盖了公式I的新化合物，其通过抑制磷酸二酯酶IV（PDE 4）提高环状腺苷酸-3'，5'-单磷酸（cAMP）水平，用于治疗包括哮喘在内的疾病，或其药物可接受的盐或水合物。本发明还涵盖了药物组合物和治疗方法。
• US6200993B1
  申请人：——

  公开号：US6200993B1

  公开（公告）日：2001-03-13