3-环丁基氧基-4-二氟甲氧基苯甲醛 | 290307-39-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 3-环丁基氧基-4-二氟甲氧基苯甲醛
• 英文名称: 3-Cyclobutoxy-4-difluoromethoxy-benzaldehyde
• 英文别名: 3-cyclobutyloxy-4-(difluoromethoxy)benzaldehyde
• CAS: 290307-39-0
• 化学式: C₁₂H₁₂F₂O₃
• 分子量: 242.222
• InChiKey: BMFYWBXIAYGBBE-UHFFFAOYSA-N

物化性质

• 沸点：
  332.3±37.0 °C(Predicted)
• 密度：
  1.292±0.06 g/cm3(Predicted)
• 溶解度：
  溶于二氯甲烷；乙酸乙酯

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-环丁基氧基-4-二氟甲氧基苯甲醛 在 lithium hydroxide 、 正丁基锂 、 氯化亚砜 、 双(三甲基硅烷基)氨基钾 作用下， 以 四氢呋喃 、 甲醇 、 六甲基磷酰三胺 、 乙醚 、 正己烷 、 二氯甲烷 为溶剂， 反应 21.83h， 生成 (+/-)-4-{2-[(3-cyclobutyloxy-4-difluoromethoxy)phenyl]-2-[5-(2-bromo)pyridyl]ethyl}pyridine
  参考文献：
  名称：

  Optimization of a Tertiary Alcohol Series of Phosphodiesterase-4 (PDE4) Inhibitors:  Structure−Activity Relationship Related to PDE4 Inhibition and Human Ether-a-go-go Related Gene Potassium Channel Binding Affinity

  摘要：

  A SAR study on the tertiary alcohol series of phosphodiesterase-4 (PDE4) inhibitors related to 1 is described. In addition to inhibitory potency against PDE4 and the lipopolysaccharide-induced production of TNFalpha in human whole blood, the binding affinity of these compounds for the human ether-a-go-go related gene (hERG) potassium channel (an in vitro measure for the potential to cause QTc prolongation) was assessed. Four key structural moieties in the molecule were studied, and the impact of the resulting modifications in modulating these activities was evaluated. From these studies, (+)-3d (L-869,298) was identified as an optimized structure with respect to PDE4 inhibitory potency, lack of binding affinity to the hERG potassium channel, and pharmacokinetic behavior. (+)-3d exhibited good in vivo efficacy in several models of pulmonary function with a wide therapeutic index with respect to emesis and prolongation of the QTc interval.

  DOI：

  10.1021/jm0204542
• 作为产物：
  描述：

  3,4-二羟基苯甲醛 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 3-环丁基氧基-4-二氟甲氧基苯甲醛
  参考文献：
  名称：

  Improving metabolic stability of phosphodiesterase-4 inhibitors containing a substituted catechol: prevention of reactive intermediate formation and covalent binding

  摘要：

  A detailed study directed towards metabolic stability optimization of the alkoxy substituents on the catechol moiety of CDP-840 is reported. Replacement of the methoxy and cyclopentyloxy substituents by cyclobutyloxy and/or difluromethoxy groups resulted in the discovery of potent and selective PDE4 inhibitors where the formation of reactive metabolites that could covalently bind to microsomal protein was significantly reduced or eliminated. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00349-9

文献信息

• Tri-aryl-substituted-ethane PDE4 inhibitors
  申请人：——

  公开号：US20020156105A1

  公开（公告）日：2002-10-24

  Novel ethanes substituted with i) a phenyl, ii) a thiazole, and iii) a pyridyl moiety are PDE4 inhibitors.

  取代基为i)苯基、ii)噻唑和iii)吡啶基的新型乙烷是PDE4抑制剂。
• [EN] PDE IV INHIBITING COMPOUNDS, COMPOSITIONS AND METHODS OF TREATMENT<br/>[FR] COMPOSES D'INHIBITION DE PDE IV, COMPOSITIONS ET METHODES DE TRAITEMENT
  申请人：MERCK FROSST CANADA INC

  公开号：WO2000050402A1

  公开（公告）日：2000-08-31

  The invention encompasses compounds 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 IV). The invention also encompasses certain pharmaceutical compositions and methods for treatment of diseases by inhibition of PDE IV, resulting in an elevation of cAMP, comprising the use of compounds of Formula (I).

  本发明涵盖了公式（I）的化合物，通过抑制磷酸二酯酶IV（PDE IV）提高环状腺苷酸-3'，5'-单磷酸（cAMP）水平，用于治疗哮喘等疾病。本发明还涵盖了某些药物组合物和通过抑制PDE IV治疗疾病的方法，导致cAMP升高，包括使用公式（I）的化合物。
• PDE IV INHIBITING COMPOUNDS, COMPOSITIONS AND METHODS OF TREATMENT
  申请人：MERCK FROSST CANADA INC.

  公开号：EP1157007A1

  公开（公告）日：2001-11-28
• TRI-ARYL-SUBSTITUTED-ETHANE PDE4 INHIBITORS
  申请人：MERCK FROSST CANADA INC.

  公开号：EP1272488A2

  公开（公告）日：2003-01-08
• US6204275B1
  申请人：——

  公开号：US6204275B1

  公开（公告）日：2001-03-20