[3,4-bis(difluoromethoxy)phenyl]-{4-[2-((2-trimethylsilylethoxy)methoxy)propane-2-yl]phenyl} chloromethane | 1055709-57-3

• 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: [3,4-bis(difluoromethoxy)phenyl]-{4-[2-((2-trimethylsilylethoxy)methoxy)propane-2-yl]phenyl} chloromethane
• 英文别名: [3,4-Bis(difluoromethoxy)phenyl]-{4-[2-((2-trimethylsilylethoxy)methoxy)propane-2-yl]phenyl}chloromethane；2-[2-[4-[[3,4-bis(difluoromethoxy)phenyl]-chloromethyl]phenyl]propan-2-yloxymethoxy]ethyl-trimethylsilane
• CAS: 1055709-57-3
• 化学式: C₂₄H₃₁ClF₄O₄Si
• 分子量: 523.04
• InChiKey: KXEJZBWZUPBARP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.78
• 重原子数：
  34
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  36.9
• 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]-{4-[2-((2-trimethylsilylethoxy)methoxy)propane-2-yl]phenyl} chloromethane 在 盐酸 、 六甲基磷酰三胺 、 lithium hydroxide 、 双(三甲基硅烷基)氨基钾 作用下， 以 四氢呋喃 、 甲醇 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：

  [3,4-bis(difluoromethoxy)phenyl]-{4-[2-((2-trimethylsilylethoxy)methoxy)propane-2yl]phenyl}methanol 在 吡啶 、 氯化亚砜 作用下， 以 甲苯 为溶剂， 反应 1.0h， 生成 [3,4-bis(difluoromethoxy)phenyl]-{4-[2-((2-trimethylsilylethoxy)methoxy)propane-2-yl]phenyl} chloromethane
  参考文献：
  名称：

  [EN] DI-ARYL-SUBSTITUTED-ETHANE PYRIDONE PDE4 INHIBITORS
  [FR] ETHANE PYRIDONE A SUBSTITUTION DIARYLE, INHIBITEURS D'ENZYME PDE4

  摘要：

  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。

  公开号：

  WO2004005258A1

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。
• 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。
• 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.