5-[1-[3,4-Bis(difluoromethoxy)phenyl]-2-(1-oxidopyridin-1-ium-4-yl)ethyl]-2-bromopyridine | 303165-23-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-[1-[3,4-Bis(difluoromethoxy)phenyl]-2-(1-oxidopyridin-1-ium-4-yl)ethyl]-2-bromopyridine
• CAS: 303165-23-3
• 化学式: C₂₀H₁₅BrF₄N₂O₃
• 分子量: 487.248
• InChiKey: LGJYEVGOHMOIOZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 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：
  56.8
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-乙基苄胺 、 5-[1-[3,4-Bis(difluoromethoxy)phenyl]-2-(1-oxidopyridin-1-ium-4-yl)ethyl]-2-bromopyridine 在 copper(l) iodide 作用下， 生成 4-{2-[3,4-Bis(difluoromethoxy)phenyl]-2-[6-(N-ethyl-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
• 作为产物：
  描述：

  (+/-)-4-{2-[3,4-bis(difluoromethoxy)phenyl]-2-[5-(2-bromo)pyridyl]ethyl}pyridine 在 MMPP 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 以93%的产率得到5-[1-[3,4-Bis(difluoromethoxy)phenyl]-2-(1-oxidopyridin-1-ium-4-yl)ethyl]-2-bromopyridine
  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

• Substituted 2-Pyridinemethanol derivatives as potent and selective phosphodiesterase-4 inhibitors
  作者：Yves Ducharme、Richard W Friesen、Marc Blouin、Bernard Côté、Daniel Dubé、Diane Ethier、Richard Frenette、France Laliberté、Joseph A Mancini、Paul Masson、Angela Styhler、Robert N Young、Yves Girard

  DOI：10.1016/s0960-894x(03)00314-7

  日期：2003.6

  synthesis and the phosphodiesterase-4 (PDE4) inhibitory activity of 2-pyridinemethanol derivatives is described. The evaluation of the structure-activity relationship (SAR) in this series of novel PDE4 inhibitors led to the identification of compound 9 which exhibits excellent in vitro activity, desirable pharmacokinetic parameters and good efficacy in animal models of bronchoconstriction.

  描述了2-吡啶甲醇衍生物的合成和磷酸二酯酶-4（PDE4）抑制活性。对这一系列新型PDE4抑制剂的构效关系（SAR）的评估导致了化合物9的鉴定，该化合物在支气管收缩动物模型中表现出优异的体外活性，理想的药代动力学参数和良好的功效。
• 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.