4-{2-[3,4-bis(difluoromethoxy)phenyl]-2-(6-amino-3-pyridyl)ethyl}pyridine-N-oxide | 306761-10-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-{2-[3,4-bis(difluoromethoxy)phenyl]-2-(6-amino-3-pyridyl)ethyl}pyridine-N-oxide
• 英文别名: 5-[1-(3,4-Bis-difluoromethoxy-phenyl)-2-(1-oxy-pyridin-4-yl)-ethyl]-pyridin-2-ylamine；5-[1-[3,4-bis(difluoromethoxy)phenyl]-2-(1-oxidopyridin-1-ium-4-yl)ethyl]pyridin-2-amine
• CAS: 306761-10-4
• 化学式: C₂₀H₁₇F₄N₃O₃
• 分子量: 423.367
• InChiKey: DAGCAMFZZCLQGL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  82.8
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  对氟苯甲酰氯 、 4-{2-[3,4-bis(difluoromethoxy)phenyl]-2-(6-amino-3-pyridyl)ethyl}pyridine-N-oxide 在 吡啶 、 乙酸铵 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 以20%的产率得到4-{2-[3,4-Bis(difluoromethoxy)phenyl]-2-{6-[4-fluorophenylamido]3-pyridyl}ethyl}pyridine-N-oxide
  参考文献：
  名称：

  Heterosubstituted pyridine derivatives as PDE4 inhibitors

  摘要：

  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。

  公开号：

  US06200993B1
• 作为产物：
  描述：

  (+/-)-[3,4-bis(difluoromethoxy)phenyl]-(2-bromopyridin-5-yl)methanol 在 palladium on activated charcoal 吡啶 、 盐酸 、 六甲基磷酰三胺 、 manganese(IV) oxide 、 lithium hydroxide 、 sodium tetrahydroborate 、 copper(l) iodide 、 氯化亚砜 、 氢气 、 双(三甲基硅烷基)氨基钾 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 生成 4-{2-[3,4-bis(difluoromethoxy)phenyl]-2-(6-amino-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.