2-(1-甲基-1-{[2-(三甲基甲硅烷基)乙氧基]甲氧基}乙基)噻唑 | 362718-78-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 2-(1-甲基-1-{[2-(三甲基甲硅烷基)乙氧基]甲氧基}乙基)噻唑
• 英文名称: 2-(1-methyl-1-{[2-(trimethylsilyl)ethoxy]methoxy}ethyl)thiazole
• 英文别名: 2-{1-methyl-1-[(2-trimethylsilylethoxy)methoxy]ethyl}thiazole；trimethyl-[2-[2-(1,3-thiazol-2-yl)propan-2-yloxymethoxy]ethyl]silane
• CAS: 362718-78-3
• 化学式: C₁₂H₂₃NO₂SSi
• 分子量: 273.472
• InChiKey: CKELMFVKHLWCTM-UHFFFAOYSA-N

物化性质

• 沸点：
  303.2±27.0 °C(Predicted)
• 密度：
  1.013±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.71
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  59.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(1-甲基-1-{[2-(三甲基甲硅烷基)乙氧基]甲氧基}乙基)噻唑 在 吡啶 、 正丁基锂 、 氯化亚砜 作用下， 以 乙醚 、 正己烷 、 甲苯 为溶剂， 反应 2.25h， 生成 2-[2-[5-[Chloro-[3-cyclobutyloxy-4-(difluoromethoxy)phenyl]methyl]-1,3-thiazol-2-yl]propan-2-yloxymethoxy]ethyl-trimethylsilane
  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：

  2-(噻唑-2-基)丙烷-2-醇 生成 2-(1-甲基-1-{[2-(三甲基甲硅烷基)乙氧基]甲氧基}乙基)噻唑
  参考文献：
  名称：

  Alkyne-aryl phosphodiesterase-4 inhibitors

  摘要：

  由公式(I)表示的化合物： 1 或其药用可接受的盐，是磷酸二酯酶4抑制剂，用于治疗哮喘和炎症。

  公开号：

  US20030114478A1

文献信息

• Use of phosphodiesterase-4 inhibitors as enhancers of cognition
  申请人：Dube Daniel

  公开号：US20060040981A1

  公开（公告）日：2006-02-23

  The present invention is directed to a method of enhancing cognition in a healthy subject comprising administering a safe cognition enhancing amount of a phosphodiesterase-4 inhibitor. In particular, this invention is directed to a method of enhancing memory, learning, retention, recall, awareness and judgement in health subjects comprising administering a safe and effective amount of a phosphodiesterase-4 inhibitor.

  本发明涉及一种增强健康受试者认知能力的方法，包括给予安全的磷酸二酯酶-4抑制剂增强认知能力的剂量。特别地，本发明涉及一种增强健康受试者记忆、学习、保留、回忆、意识和判断力的方法，包括给予安全有效的磷酸二酯酶-4抑制剂的剂量。
• Use of pde4 inhibitors as adjunct therapy for psychiatric disorders
  申请人：Scolnick M. Edward

  公开号：US20060069115A1

  公开（公告）日：2006-03-30

  The use of a PDE4 inhibitor in conjunction with psychotherapy provides enhanced therapeutic results in the treatment of psychiatric disorders including, for example, specific phobias, panic disorders, anxiety disorders including posttraumatic stress disorders, and obsessive-compulsive disorder.

  在治疗精神障碍，例如特定恐惧症、惊恐障碍、包括创伤后应激障碍和强迫症的焦虑障碍中，与心理治疗同时使用PDE4抑制剂可以提供增强的治疗效果。
• 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
  作者：Richard W. Friesen、Yves Ducharme、Richard G. Ball、Marc Blouin、Louise Boulet、Bernard Côté、Richard Frenette、Mario Girard、Daniel Guay、Zheng Huang、Thomas R. Jones、France Laliberté、Joseph J. Lynch、Joseph Mancini、Evelyn Martins、Paul Masson、Eric Muise、Douglas J. Pon、Peter K. S. Siegl、Angela Styhler、Nancy N. Tsou、Mervyn J. Turner、Robert N. Young、Yves Girard

  DOI：10.1021/jm0204542

  日期：2003.6.1

  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.
• Alkyne-aryl phosphodiesterase-4 inhibitors
  申请人：——

  公开号：US20030114478A1

  公开（公告）日：2003-06-19

  Compounds represented by Formula (I): 1 or a pharmaceutically acceptable salt thereof, are phosphodiesterase 4 inhibitors useful in the treatment of asthma and inflammation.

  由公式(I)表示的化合物： 1 或其药用可接受的盐，是磷酸二酯酶4抑制剂，用于治疗哮喘和炎症。