(4-bromophenethoxy)trimethylsilane | 86605-94-9

• 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: (4-bromophenethoxy)trimethylsilane
• 英文别名: 4-Bromophenethyl alcohol, TMS derivative；2-(4-bromophenyl)ethoxy-trimethylsilane
• CAS: 86605-94-9
• 化学式: C₁₁H₁₇BrOSi
• 分子量: 273.245
• InChiKey: JKUSCWVQSVIEAF-UHFFFAOYSA-N

物化性质

• 沸点：
  275.3±23.0 °C(Predicted)
• 密度：
  1.187±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.84
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-[(S)-1-(4-fluorophenyl)ethylamino]-5-methylthiazol-4(5H)-one 、 (4-bromophenethoxy)trimethylsilane 在 tris-(dibenzylideneacetone)dipalladium(0) 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 lithium hexamethyldisilazane 作用下， 以 甲苯 为溶剂， 以31%的产率得到2-[(S)-1-(4-fluorophenyl)ethylamino]-5-methyl-5-{4-[2-(trimethylsilyloxy)ethyl]phenyl}thiazol-4(5H)-one
  参考文献：
  名称：

  Further Studies with the 2-Amino-1,3-thiazol-4(5H)-one Class of 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors: Reducing Pregnane X Receptor Activity and Exploring Activity in a Monkey Pharmacodynamic Model

  摘要：

  A series of compounds containing the 2-amino-1,3-thiazol-4(5H)-one core were found to be potent inhibitors of the enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1). One of our lead compounds from this series activated the human nuclear xenobiotic receptor, pregnane X receptor (PXR). To try and mitigate the PXR activity, we prepared analogues of our lead series that contained polar groups on the right-hand side of the thiazolone. Several analogues containing amides or alcohols appended to the C-5 position of the thiazolone showed a significant reduction in PXR activity. Through these structure-activity efforts, a compound containing a tert-alcohol group off the C-5 position, analogue (S)-33a, Was found to have an 11 beta-HSD1 K(i) = 35 nM and negligible PXR activity. Compound (S)-33a was advanced into a pharmacodynamic model in cynomolgus monkeys, where it inhibited adipose 11 beta-HSD1 activity after being orally administered.

  DOI：

  10.1021/jm801073z
• 作为产物：
  描述：

  三甲基氯硅烷 、 4-溴苯乙醇 在 N,N-二异丙基乙胺 、 potassium carbonate 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以84%的产率得到(4-bromophenethoxy)trimethylsilane
  参考文献：
  名称：

  Further Studies with the 2-Amino-1,3-thiazol-4(5H)-one Class of 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors: Reducing Pregnane X Receptor Activity and Exploring Activity in a Monkey Pharmacodynamic Model

  摘要：

  A series of compounds containing the 2-amino-1,3-thiazol-4(5H)-one core were found to be potent inhibitors of the enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1). One of our lead compounds from this series activated the human nuclear xenobiotic receptor, pregnane X receptor (PXR). To try and mitigate the PXR activity, we prepared analogues of our lead series that contained polar groups on the right-hand side of the thiazolone. Several analogues containing amides or alcohols appended to the C-5 position of the thiazolone showed a significant reduction in PXR activity. Through these structure-activity efforts, a compound containing a tert-alcohol group off the C-5 position, analogue (S)-33a, Was found to have an 11 beta-HSD1 K(i) = 35 nM and negligible PXR activity. Compound (S)-33a was advanced into a pharmacodynamic model in cynomolgus monkeys, where it inhibited adipose 11 beta-HSD1 activity after being orally administered.

  DOI：

  10.1021/jm801073z