[3,4-Bis(difluoromethoxy)phenyl]-(6-bromo-pyridin-3-yl)methanone | 303165-21-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [3,4-Bis(difluoromethoxy)phenyl]-(6-bromo-pyridin-3-yl)methanone
• 英文别名: [3,4-Bis(difluoromethoxy)phenyl]-(6-bromo-3-pyridyl)methanone；[3,4-Bis(difluoromethoxy)phenyl]-(6-bromopyridin-3-yl)methanone
• CAS: 303165-21-1
• 化学式: C₁₄H₈BrF₄NO₃
• 分子量: 394.12
• InChiKey: WSHWAKCLRQUSAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  48.4
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  [3,4-Bis(difluoromethoxy)phenyl]-(6-bromo-pyridin-3-yl)methanone 在 sodium tetrahydroborate 、 copper(l) iodide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 (3,4-Bis-difluoromethoxy-phenyl)-{6-[methyl-((R)-1-phenyl-ethyl)-amino]-pyridin-3-yl}-methanol
  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 manganese(IV) oxide 作用下， 以 二氯甲烷 为溶剂， 以88%的产率得到[3,4-Bis(difluoromethoxy)phenyl]-(6-bromo-pyridin-3-yl)methanone
  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

• US6180650
  申请人：——

  公开号：——

  公开（公告）日：——
• US6180650B1
  申请人：——

  公开号：US6180650B1

  公开（公告）日：2001-01-30
• US6200993B1
  申请人：——

  公开号：US6200993B1

  公开（公告）日：2001-03-13
• 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.