4-{2-[3,4-Bis(difluoromethoxy)phenyl]-2-[6-(N-methyl-N-phenylamino)3-pyridyl]ethyl}pyridine | 306761-25-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 4-{2-[3,4-Bis(difluoromethoxy)phenyl]-2-[6-(N-methyl-N-phenylamino)3-pyridyl]ethyl}pyridine
• 英文别名: 5-[1-[3,4-bis(difluoromethoxy)phenyl]-2-pyridin-4-ylethyl]-N-methyl-N-phenylpyridin-2-amine
• CAS: 306761-25-1
• 化学式: C₂₇H₂₃F₄N₃O₂
• 分子量: 497.492
• InChiKey: YLADAXXJNSQNSA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  47.5
• 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-phenylamino)3-pyridyl]ethyl}pyridine 在 MMPP 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-phenylamino)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 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 、 双(三甲基硅烷基)氨基钾 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 生成 4-{2-[3,4-Bis(difluoromethoxy)phenyl]-2-[6-(N-methyl-N-phenylamino)3-pyridyl]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

• US6200993B1
  申请人：——

  公开号：US6200993B1

  公开（公告）日：2001-03-13