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

文献信息

• Further Studies with the 2-Amino-1,3-thiazol-4(5<i>H</i>)-one Class of 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors: Reducing Pregnane X Receptor Activity and Exploring Activity in a Monkey Pharmacodynamic Model
  作者：Christopher Fotsch、Michael D. Bartberger、Eric A. Bercot、Michelle Chen、Rod Cupples、Maury Emery、Jenne Fretland、Anil Guram、Clarence Hale、Nianhe Han、Dean Hickman、Randall W. Hungate、Michael Hayashi、Renee Komorowski、Qingyian Liu、Guy Matsumoto、David J. St. Jean、Stefania Ursu、Murielle Véniant、Guifen Xu、Qiuping Ye、Chester Yuan、Jiandong Zhang、Xiping Zhang、Hua Tu、Minghan Wang

  DOI：10.1021/jm801073z

  日期：2008.12.25

  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.