2-[(S)-1-(4-fluorophenyl)ethylamino]-5-methyl-5-{4-[2-(trimethylsilyloxy)ethyl]phenyl}thiazol-4(5H)-one | 1092660-17-7

• 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: 2-[(S)-1-(4-fluorophenyl)ethylamino]-5-methyl-5-{4-[2-(trimethylsilyloxy)ethyl]phenyl}thiazol-4(5H)-one
• 英文别名: 2-[(1S)-1-(4-fluorophenyl)ethyl]imino-5-methyl-5-[4-(2-trimethylsilyloxyethyl)phenyl]-1,3-thiazolidin-4-one
• CAS: 1092660-17-7
• 化学式: C₂₃H₂₉FN₂O₂SSi
• 分子量: 444.645
• InChiKey: RQCHJRQHTGDANH-GZWBLTSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.42
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  76
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-[(S)-1-(4-fluorophenyl)ethylamino]-5-methyl-5-{4-[2-(trimethylsilyloxy)ethyl]phenyl}thiazol-4(5H)-one 在 甲醇 、 potassium carbonate 作用下， 反应 1.0h， 以93%的产率得到2-{(S)-[1-(4-fluorophenyl)ethyl]amino}-5-[4-(2-hydroxyethyl)phenyl]-5-methyl-1,3-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：

  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