[4-[1-[3,4-Bis(difluoromethoxy)phenyl]-2-(1-oxidopyridin-1-ium-4-yl)ethyl]phenyl]methanol | 474500-05-5

• 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-[1-[3,4-Bis(difluoromethoxy)phenyl]-2-(1-oxidopyridin-1-ium-4-yl)ethyl]phenyl]methanol
• CAS: 474500-05-5
• 化学式: C₂₂H₁₉F₄NO₄
• 分子量: 437.391
• InChiKey: XGBRBTLQKWWZHQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  64.2
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  [4-[1-[3,4-Bis(difluoromethoxy)phenyl]-2-(1-oxidopyridin-1-ium-4-yl)ethyl]phenyl]methanol 在 manganese(IV) oxide 、 正丁基锂 、 cerium(III) chloride 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 生成
  参考文献：
  名称：

  Discovery of L-791,943: A potent, selective, non emetic and orally active phosphodiesterase-4 inhibitor

  摘要：

  Structure-activity relationship studies directed toward improving the potency and metabolic stability of CDP-840 (3) resulted in the discovery of L-791,943 (1 In) as a potent (HWB TNF-alpha = 0.67 muM) and orally active phosphodiesterase type 4 (PDE4) inhibitor. This compound, which bears a stable bis-difluoromethoxy catechol and a pendant hexafluorocarbinol, exhibited a long half-life in rat and in squirrel monkey. It is well tolerated in ferret with an emetic threshold greater than 30 mg/kg (po) and was found to be active in the ovalbumin-induced bronchoconstriction model in guinea pig and in the ascaris-induced bronchoconstriction models in sheep and squirrel monkey. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00190-7
• 作为产物：
  描述：

  在 MMPP 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 以93%的产率得到[4-[1-[3,4-Bis(difluoromethoxy)phenyl]-2-(1-oxidopyridin-1-ium-4-yl)ethyl]phenyl]methanol
  参考文献：
  名称：

  Discovery of L-791,943: A potent, selective, non emetic and orally active phosphodiesterase-4 inhibitor

  摘要：

  Structure-activity relationship studies directed toward improving the potency and metabolic stability of CDP-840 (3) resulted in the discovery of L-791,943 (1 In) as a potent (HWB TNF-alpha = 0.67 muM) and orally active phosphodiesterase type 4 (PDE4) inhibitor. This compound, which bears a stable bis-difluoromethoxy catechol and a pendant hexafluorocarbinol, exhibited a long half-life in rat and in squirrel monkey. It is well tolerated in ferret with an emetic threshold greater than 30 mg/kg (po) and was found to be active in the ovalbumin-induced bronchoconstriction model in guinea pig and in the ascaris-induced bronchoconstriction models in sheep and squirrel monkey. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00190-7

文献信息

• Discovery of L-791,943: A potent, selective, non emetic and orally active phosphodiesterase-4 inhibitor
  作者：Daniel Guay、Pierre Hamel、Marc Blouin、Christine Brideau、Chi Chung Chan、Nathalie Chauret、Yves Ducharme、Zheng Huang、Mario Girard、Tom R. Jones、France Laliberté、Paul Masson、Malia McAuliffe、Hanna Piechuta、José Silva、Robert N. Young、Yves Girard

  DOI：10.1016/s0960-894x(02)00190-7

  日期：2002.6

  Structure-activity relationship studies directed toward improving the potency and metabolic stability of CDP-840 (3) resulted in the discovery of L-791,943 (1 In) as a potent (HWB TNF-alpha = 0.67 muM) and orally active phosphodiesterase type 4 (PDE4) inhibitor. This compound, which bears a stable bis-difluoromethoxy catechol and a pendant hexafluorocarbinol, exhibited a long half-life in rat and in squirrel monkey. It is well tolerated in ferret with an emetic threshold greater than 30 mg/kg (po) and was found to be active in the ovalbumin-induced bronchoconstriction model in guinea pig and in the ascaris-induced bronchoconstriction models in sheep and squirrel monkey. (C) 2002 Elsevier Science Ltd. All rights reserved.