4-{2-[3,4-Bis(difluoromethoxy)phenyl]-2-[6-(N-methyl-N-benzylamino)3-pyridyl]ethyl}pyridine-N-oxide

• 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-(N-methyl-N-benzylamino)3-pyridyl]ethyl}pyridine-N-oxide
• 英文别名: N-benzyl-5-[1-[3,4-bis(difluoromethoxy)phenyl]-2-(1-oxidopyridin-1-ium-4-yl)ethyl]-N-methylpyridin-2-amine
• 化学式: C₂₈H₂₅F₄N₃O₃
• 分子量: 527.518
• InChiKey: PYMWHQDWPKXMFS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  38
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  60
• 氢给体数：
  0
• 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-(N-methyl-N-benzylamino)3-pyridyl]ethyl}pyridine-N-oxide 、 、 盐酸 在 1,4-二氧六环 、 乙醚 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.5h， 以to afford the title compound as a yellow solid (160 mg, 94%)的产率得到4-{2-[3,4-Bis(difluoromethoxy)phenyl]-2-[6-(N-methyl-N-benzylamino)3-pyridyl}ethyl}pyridine-N-oxide hydrochloride
  参考文献：
  名称：

  Heterosubstituted pyridine derivatives as PDE4 inhibitors

  摘要：

  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。

  公开号：

  US06200993B1
• 作为产物：
  描述：

  (+/-)-4-{2-[3,4-bis(difluoromethoxy)phenyl]-2-[5-(2-bromo)pyridyl]ethyl}pyridine 在 copper(l) iodide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 4-{2-[3,4-Bis(difluoromethoxy)phenyl]-2-[6-(N-methyl-N-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

文献信息

• US6200993B1
  申请人：——

  公开号：US6200993B1

  公开（公告）日：2001-03-13
• 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.

  该发明涵盖了一种新型化合物，其化学式为I，可用于治疗包括哮喘在内的疾病，通过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）的水平，或其药用可接受盐或水合物。该发明还涵盖了用于治疗的药物组合物和方法。
• Substituted aminopyridines as potent and selective phosphodiesterase-4 inhibitors
  作者：Bernard Côté、Richard Frenette、Sylvie Prescott、Marc Blouin、Christine Brideau、Yves Ducharme、Richard W. Friesen、France Laliberté、Paul Masson、Angela Styhler、Yves Girard

  DOI：10.1016/s0960-894x(02)01030-2

  日期：2003.2

  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.