2-[(S)-1-(4-fluorophenyl)ethylamino]-5-methyl-5-[4-(morpholine-4-carbonyl)phenyl]thiazol-4(5H)-one | 1092660-06-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: 2-[(S)-1-(4-fluorophenyl)ethylamino]-5-methyl-5-[4-(morpholine-4-carbonyl)phenyl]thiazol-4(5H)-one
• 英文别名: 2-[(S)-1-(4-Fluorophenyl)ethylamino]-5-methyl-5-[4-(morpholine-4-carbonyl)phenyl]thiazol-4(5H)-one；2-[(1S)-1-(4-fluorophenyl)ethyl]imino-5-methyl-5-[4-(morpholine-4-carbonyl)phenyl]-1,3-thiazolidin-4-one
• CAS: 1092660-06-4
• 化学式: C₂₃H₂₄FN₃O₃S
• 分子量: 441.526
• InChiKey: HSWRSJVMGAZCAR-NGMICRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  96.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  吗啉 、 4-{2-[(S)-1-(4-fluorophenyl)ethylamino]-5-methyl-4-oxo-4,5-dihydrothiazol-5-yl}benzoic acid 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以91%的产率得到2-[(S)-1-(4-fluorophenyl)ethylamino]-5-methyl-5-[4-(morpholine-4-carbonyl)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