1,1,1,3,3,3-hexafluoro-2-(1,3-thiazol-2-yl)propan-2-ol | 362718-79-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1,1,1,3,3,3-hexafluoro-2-(1,3-thiazol-2-yl)propan-2-ol
• 英文别名: 2-Thiazolemethanol, alpha,alpha-bis(trifluoromethyl)-
• CAS: 362718-79-4
• 化学式: C₆H₃F₆NOS
• 分子量: 251.152
• InChiKey: YFNPVQDQULAPPS-UHFFFAOYSA-N

物化性质

• 沸点：
  213.3±40.0 °C(Predicted)
• 密度：
  1.645±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  61.4
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1,1,1,3,3,3-hexafluoro-2-(1,3-thiazol-2-yl)propan-2-ol 在 吡啶 、 二溴亚砜 、 正丁基锂 、 N,N-二异丙基乙胺 作用下， 以 乙醚 、 正己烷 、 二氯甲烷 、 甲苯 为溶剂， 反应 53.0h， 生成 5-[Bromo-(3-cyclopropoxy-4-difluoromethoxy-phenyl)-methyl]-2-[2,2,2-trifluoro-1-trifluoromethyl-1-(2-trimethylsilanyl-ethoxymethoxy)-ethyl]-thiazole
  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：

  噻唑 、 六氟丙酮 在 正丁基锂 作用下， 以 乙醚 、 正己烷 为溶剂， 反应 1.25h， 以78 g的产率得到1,1,1,3,3,3-hexafluoro-2-(1,3-thiazol-2-yl)propan-2-ol
  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

文献信息

• Tri-aryl-substituted-ethane PDE4 inhibitors
  申请人：——

  公开号：US20020156105A1

  公开（公告）日：2002-10-24

  Novel ethanes substituted with i) a phenyl, ii) a thiazole, and iii) a pyridyl moiety are PDE4 inhibitors.

  取代基为i)苯基、ii)噻唑和iii)吡啶基的新型乙烷是PDE4抑制剂。
• Practical synthesis of a highly functionalized thiazole ketone
  作者：Lisa F Frey、Karen M Marcantonio、Cheng-yi Chen、Debra J Wallace、Jerry A Murry、Lushi Tan、Weirong Chen、Ulf H Dolling、Edward J.J Grabowski

  DOI：10.1016/s0040-4020(03)00878-0

  日期：2003.8

  Compound 1 is a uniquely substituted ketone prepared via addition of a thiazole anion to an aromatic nitrile in good overall yield. An exploration into the generality of the addition of thiazole anions to nitriles allowed us to make a variety of thiazole ketones in good to excellent yields. The non-odorous thiolate-mediated demethylation reaction used in the synthesis of 1 is also presented. (C) 2003 Elsevier Ltd. All rights reserved.
• TRI-ARYL-SUBSTITUTED-ETHANE PDE4 INHIBITORS
  申请人：Merck Frosst Canada & Co.

  公开号：EP1272488B1

  公开（公告）日：2006-03-22
• US6399636B2
  申请人：——

  公开号：US6399636B2

  公开（公告）日：2002-06-04
• US6639077B2
  申请人：——

  公开号：US6639077B2

  公开（公告）日：2003-10-28