(R)-4-{2-(3-Cyclopentyloxy-4-methoxyphenyl)-2-[4-(2-(2-(trimethylsilyl)ethoxymethoxy)-1,1,1,3,3,3-hexafluoropropan-2-yl)phenyl]ethyl}pyridine | 192767-05-8

• 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: (R)-4-{2-(3-Cyclopentyloxy-4-methoxyphenyl)-2-[4-(2-(2-(trimethylsilyl)ethoxymethoxy)-1,1,1,3,3,3-hexafluoropropan-2-yl)phenyl]ethyl}pyridine
• 英文别名: 2-[[2-[4-[(1R)-1-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyridin-4-ylethyl]phenyl]-1,1,1,3,3,3-hexafluoropropan-2-yl]oxymethoxy]ethyl-trimethylsilane
• CAS: 192767-05-8
• 化学式: C₃₄H₄₁F₆NO₄Si
• 分子量: 669.78
• InChiKey: FPOFPQVSASVCDR-GDLZYMKVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.43
• 重原子数：
  46
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (R)-4-{2-(3-Cyclopentyloxy-4-methoxyphenyl)-2-[4-(2-(2-(trimethylsilyl)ethoxymethoxy)-1,1,1,3,3,3-hexafluoropropan-2-yl)phenyl]ethyl}pyridine 在 10% palladium on active carbon N-碘代丁二酰亚胺 、 四丁基氟化铵 、 氢气 、 三乙胺 、 三氟乙酸 作用下， 以 甲醇 、 氯仿 、 乙酸乙酯 为溶剂， 生成 2-[4-[(1R)-1-(5-cyclopentyloxy-4-methoxy-2-tritiophenyl)-2-pyridin-4-ylethyl]phenyl]-1,1,1,3,3,3-hexafluoropropan-2-ol
  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
• 作为产物：
  描述：

  2-(4-bromophenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol 在 lithium hydroxide 、 magnesium 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (R)-4-{2-(3-Cyclopentyloxy-4-methoxyphenyl)-2-[4-(2-(2-(trimethylsilyl)ethoxymethoxy)-1,1,1,3,3,3-hexafluoropropan-2-yl)phenyl]ethyl}pyridine
  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 ethane derivatives as PDE IV inhibitors
  申请人：Merck Frosst Canada, Inc.

  公开号：US05710170A1

  公开（公告）日：1998-01-20

  The invention encompasses the novel compound 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). ##STR1## 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.

  该发明涵盖了化合物I的新颖结构，可用于治疗包括哮喘在内的疾病，通过通过抑制磷酸二酯酶IV（PDE IV）提高环状腺苷-3'，5'-单磷酸（cAMP）的水平。 该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，包括使用化合物I的用途。
• Improving metabolic stability of phosphodiesterase-4 inhibitors containing a substituted catechol: prevention of reactive intermediate formation and covalent binding
  作者：Nathalie Chauret、Daniel Guay、Chun Li、Stephen Day、José Silva、Marc Blouin、Yves Ducharme、James A. Yergey、Deborah A. Nicoll-Griffith

  DOI：10.1016/s0960-894x(02)00349-9

  日期：2002.8

  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.