(4-aminophenyl)-(4aSR,8aSR)octahydrobenzo[1,4]oxazin-4-ylmethanone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: (4-aminophenyl)-(4aSR,8aSR)octahydrobenzo[1,4]oxazin-4-ylmethanone
• 英文别名: [(4aR,8aR)-2,3,4a,5,6,7,8,8a-octahydrobenzo[b][1,4]oxazin-4-yl]-(4-aminophenyl)methanone
• 化学式: C₁₅H₂₀N₂O₂
• 分子量: 260.336
• InChiKey: VLJNDNUWYGEPHL-ZIAGYGMSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.05
• 重原子数：
  19.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  55.56
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (4-aminophenyl)-(4aSR,8aSR)octahydrobenzo[1,4]oxazin-4-ylmethanone 、 2,4-二氯苯甲酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以81%的产率得到2,4-dichloro-N-[4-((4aSR,8aSR)octahydrobenzo[1,4]oxazine-4-carbonyl)phenyl]benzamide
  参考文献：
  名称：

  Perhydroquinolylbenzamides as Novel Inhibitors of 11β-Hydroxysteroid Dehydrogenase Type 1

  摘要：

  High-throughput screening identified 5 as a weak inhibitor of 11 beta-HSD1. Optimization of the structure led to a series of perhydroquinolylbenzamides, some with low nanomolar inhibitory potency. A tertiary benzamide is required for biological activity and substitution of the terminal benzamide with either electron-donating or -withdrawing groups is tolerated. The majority of the compounds show selectivity of > 20 to > 700-fold over 11 beta-HSD2. Analogues which showed >50% inhibition of 11 beta-HSD1 at 1 mu M in an cellular assay were screened in an ADX mouse model. A maximal response of > 70% reduction of liver corticosterone levels was observed for three compounds; 9m, 25 and 49.

  DOI：

  10.1021/jm058228q
• 作为产物：
  描述：

  (4-nitrophenyl)-(4aSR,8aSR)-octahydrobenzo[1,4]oxazin-4-ylmethanone 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以85%的产率得到(4-aminophenyl)-(4aSR,8aSR)octahydrobenzo[1,4]oxazin-4-ylmethanone
  参考文献：
  名称：

  Perhydroquinolylbenzamides as Novel Inhibitors of 11β-Hydroxysteroid Dehydrogenase Type 1

  摘要：

  High-throughput screening identified 5 as a weak inhibitor of 11 beta-HSD1. Optimization of the structure led to a series of perhydroquinolylbenzamides, some with low nanomolar inhibitory potency. A tertiary benzamide is required for biological activity and substitution of the terminal benzamide with either electron-donating or -withdrawing groups is tolerated. The majority of the compounds show selectivity of > 20 to > 700-fold over 11 beta-HSD2. Analogues which showed >50% inhibition of 11 beta-HSD1 at 1 mu M in an cellular assay were screened in an ADX mouse model. A maximal response of > 70% reduction of liver corticosterone levels was observed for three compounds; 9m, 25 and 49.

  DOI：

  10.1021/jm058228q

文献信息

• Perhydroquinolylbenzamides as Novel Inhibitors of 11β-Hydroxysteroid Dehydrogenase Type 1
  作者：Gary M. Coppola、Paivi J. Kukkola、James L. Stanton、Alan D. Neubert、Nicholas Marcopulos、Natalie A. Bilci、Hua Wang、Hollis C. Tomaselli、Jenny Tan、Thomas D. Aicher、Douglas C. Knorr、Arco Y. Jeng、Beatriz Dardik、Ricardo E. Chatelain

  DOI：10.1021/jm058228q

  日期：2005.10.1

  High-throughput screening identified 5 as a weak inhibitor of 11 beta-HSD1. Optimization of the structure led to a series of perhydroquinolylbenzamides, some with low nanomolar inhibitory potency. A tertiary benzamide is required for biological activity and substitution of the terminal benzamide with either electron-donating or -withdrawing groups is tolerated. The majority of the compounds show selectivity of > 20 to > 700-fold over 11 beta-HSD2. Analogues which showed >50% inhibition of 11 beta-HSD1 at 1 mu M in an cellular assay were screened in an ADX mouse model. A maximal response of > 70% reduction of liver corticosterone levels was observed for three compounds; 9m, 25 and 49.