3-环丙氧基-4-二氟甲氧基-苯甲醛 | 362718-98-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 3-环丙氧基-4-二氟甲氧基-苯甲醛
• 英文名称: 3-cyclopropyloxy-4-difluoromethoxybenzaldehyde
• 英文别名: 3-cyclopropyloxy-4-(difluoromethoxy)benzaldehyde
• CAS: 362718-98-7
• 化学式: C₁₁H₁₀F₂O₃
• 分子量: 228.195
• InChiKey: QQIQCVYBOCMZBR-UHFFFAOYSA-N

物化性质

• 沸点：
  316.0±37.0 °C(Predicted)
• 密度：
  1.344±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 海关编码：
  2913000090

反应信息

• 作为反应物：
  描述：

  3-环丙氧基-4-二氟甲氧基-苯甲醛 、 2-{1-trifluoromethyl-1-[(2-trimethylsilylethoxy)methoxy]-2,2,2-trifluoroethyl}thiazole 在 正丁基锂 作用下， 以 乙醚 、 正己烷 为溶剂， 反应 4.0h， 以94%的产率得到(+/-)-[(3-cyclopropyloxy-4-difluoromethoxy)phenyl]{2-[(1-trifluoromethyl-1-(2-trimethylsilylethoxy)methoxy)-2,2,2-trifluoro]ethylthiazol-5-yl}methanol
  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-Cyclopropyloxy-4-difluoromethoxybenzyl alcohol 在 二氧化锰 乙酸乙酯 、 二氯甲烷 、 乙醇 、 甲苯 、 silica gel 、 ethyl acetate n-hexane 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 48.0h， 以Flash chromatography of the residue (silica gel; hexane/ethyl acetate 3:1 to 7:3) provided the 3-Cyclopropyloxy-4-difluoromethoxybenzaldehyde compound (3 1 g)的产率得到3-环丙氧基-4-二氟甲氧基-苯甲醛
  参考文献：
  名称：

  Tri-aryl-substituted-ethane PDE4 inhibitors

  摘要：

  用i)苯基，ii)噻唑基和iii)吡啶基取代的新型乙烷类物质是PDE4抑制剂。

  公开号：

  US20020156105A1

文献信息

• [EN] DI-ARYL-SUBSTITUTED-ETHANE PYRIDONE PDE4 INHIBITORS<br/>[FR] ETHANE PYRIDONE A SUBSTITUTION DIARYLE, INHIBITEURS D'ENZYME PDE4
  申请人：MERCK FROSST CANADA INC

  公开号：WO2004005258A1

  公开（公告）日：2004-01-15

  Di-aryl substituted ethane pyridones, particularly ethane pyridones substituted with i) a phenyl, ii) a pyridyl, iii) a thiazole, iv) a pyrimidinyl, v) a pyridazinyl, vi) a furyl, vii) a thienyl, viii) an oxazolyl, ix) an isoxazolyl, or x) an isothiazolyl moiety are phosphodiesterase-4 inhibitors useful in the treatment or prevention of asthma; chronic bronchitis; chronic obstructive pulmonary disease; adult respiratory distress syndrome; infant respiratory distress syndrome; cough; chronic obstructive pulmonary disease in animals; adult respiratory distress syndrome; ulcerative colitis; Crohn's disease; hypersecretion of gastric acid; bacterial, fungal or viral induced sepsis or septic shock; endotoxic shock; laminitis or colic in horses; spinal cord trauma; head injury; neurogenic inflammation; pain; reperfusion injury of the brain; psoriatic arthritis; rheumatoid arthritis; ankylosing spondylitis; osteoarthritis; inflammation; or cytokine-mediated chronic tissue degeneration. Formula (I) wherein X is phenyl, pyridinyl, thiazolyl, pyrimidinyl, pyridazinyl, furyl, thienyl, oxazolyl, isoxazolyl, isothiazolyl.

  二芳基取代的乙烷吡啶酮，特别是取代有i) 苯基、ii) 吡啶基、iii) 噻唑基、iv) 嘧啶基、v) 吡啉基、vi) 呋喃基、vii) 噻吩基、viii) 噁唑基、ix) 异噁唑基或x) 异硫唑基基团的乙烷吡啶酮是磷酸二酯酶-4抑制剂，可用于治疗或预防哮喘；慢性支气管炎；慢性阻塞性肺疾病；成人呼吸窘迫综合征；婴儿呼吸窘迫综合征；咳嗽；动物慢性阻塞性肺疾病；成人呼吸窘迫综合征；溃疡性结肠炎；克罗恩病；胃酸过多；细菌、真菌或病毒引起的败血症或感染性休克；内毒素性休克；马的蹄受损或腹痛；脊髓创伤；头部受伤；神经源性炎症；疼痛；脑再灌注损伤；银屑病性关节炎；类风湿关节炎；强直性脊柱炎；骨关节炎；炎症；或细胞因子介导的慢性组织退化。式(I)中X为苯基、吡啶基、噻唑基、嘧啶基、吡啉基、呋喃基、噻吩基、噁唑基、异噁唑基或异硫唑基。
• [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。
• Di-aryl-substituted-ethan pyridone pde4 inhibitors
  申请人：Cote Bernard

  公开号：US20060004056A1

  公开（公告）日：2006-01-05

  Di-aryl substituted ethane pyridones, particularly ethane pyridones substituted with i) a phenyl, ii) a pyridyl, iii) a thiazole, iv) a pyrimidinyl, v) a pyridazinyl, vi) a furyl, vii) a thienyl, viii) an oxazolyl, ix) an isoxazolyl, or x) an isothiazolyl moiety are phosphodiesterase-4 inhibitors useful in the treatment or prevention of asthma; chronic bronchitis; chronic obstructive pulmonary disease; adult respiratory distress syndrome; infant respiratory distress syndrome; cough; chronic obstructive pulmonary disease in animals; adult respiratory distress syndrome; ulcerative colitis; Crohn's disease; hypersecretion of gastric acid; bacterial, fungal or viral induced sepsis or septic shock; endotoxic shock; laminitis or colic in horses; spinal cord trauma; head injury; neurogenic inflammation; pain; reperfusion injury of the brain; psoriatic arthritis; rheumatoid arthritis; ankylosing spondylitis; osteoarthritis; inflammation; or cytokine-mediated chronic tissue degeneration.

  二芳基取代乙烯吡啶酮，特别是乙烯吡啶酮取代i）苯基，ii）吡啶基，iii）噻唑基，iv）嘧啶基，v）吡嗪基，vi）呋喃基，vii）噻吩基，viii）噁唑基，ix）异噁唑基，或x）异硫氰酰基基团是磷酸二酯酶-4抑制剂，可用于治疗或预防哮喘；慢性支气管炎；慢性阻塞性肺疾病；成人呼吸窘迫综合征；婴儿呼吸窘迫综合征；咳嗽；动物慢性阻塞性肺疾病；成人呼吸窘迫综合征；溃疡性结肠炎；克罗恩病；胃酸过多；细菌、真菌或病毒引起的败血症或感染性休克；内毒素性休克；马蹄褥疮或腹绞痛；脊髓创伤；头部损伤；神经源性炎症；疼痛；脑再灌注损伤；银屑病性关节炎；类风湿性关节炎；强直性脊柱炎；骨关节炎；炎症或细胞因子介导的慢性组织退化。
• 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