硅烷,[2-[[1-(4-溴苯基)-2,2,2-三氟-1-(三氟甲基)乙氧基]甲氧基]乙基]三甲基- | 192767-03-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 硅烷,[2-[[1-(4-溴苯基)-2,2,2-三氟-1-(三氟甲基)乙氧基]甲氧基]乙基]三甲基-
• 英文名称: 2-(4-bromophenyl)-2-[2-(trimethylsilyl)ethoxymethoxy]-1,1,1,3,3,3-hexafluoropropane
• 英文别名: 2-[[2-(4-bromophenyl)-1,1,1,3,3,3-hexafluoropropan-2-yl]oxymethoxy]ethyl-trimethylsilane
• CAS: 192767-03-6
• 化学式: C₁₅H₁₉BrF₆O₂Si
• 分子量: 453.295
• InChiKey: UPYLMAWVDTTZQL-UHFFFAOYSA-N

物化性质

• 沸点：
  341.2±42.0 °C(Predicted)
• 密度：
  1.348±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  硅烷,[2-[[1-(4-溴苯基)-2,2,2-三氟-1-(三氟甲基)乙氧基]甲氧基]乙基]三甲基- 在 吡啶 、 正丁基锂 、 氯化亚砜 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 生成 2-[[2-[4-[[3,4-Bis(difluoromethoxy)phenyl]-chloromethyl]phenyl]-1,1,1,3,3,3-hexafluoropropan-2-yl]oxymethoxy]ethyl-trimethylsilane
  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：

  1,4-二溴苯 在 正丁基锂 、 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 硅烷,[2-[[1-(4-溴苯基)-2,2,2-三氟-1-(三氟甲基)乙氧基]甲氧基]乙基]三甲基-
  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

• 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。
• 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.
• 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.
• Substituted 4-(2,2-diphenylethyl)pyridine-N-oxides as phosphodiesterase-4 inhibitors: SAR study directed toward the improvement of pharmacokinetic parameters
  作者：Richard Frenette、Marc Blouin、Christine Brideau、Nathalie Chauret、Yves Ducharme、Richard W. Friesen、Pierre Hamel、Tom R. Jones、France Laliberté、Chun Li、Paul Masson、Malia McAuliffe、Yves Girard

  DOI：10.1016/s0960-894x(02)00615-7

  日期：2002.10

  A detailed SAR study directed toward the optimization of pharmacokinetic parameters for analogues of L-791,943 is reported. The introduction of a soft metabolic site on this structure permitted the identification of L-826,141 as a potent phosphodiesterase type 4 (PDE4) inhibitor that is well absorbed and that presents a shorter half-life than L-791,943 in a variety of animal species. The efficacy of L-826,141 is also demonstrated in different in vivo models. (C) 2002 Elsevier Science Ltd. All rights reserved.