(5aR,7aR,7bS,9aS,12S,13aR,15aR,15bS)-5,5,7a,7b,9a,12,15b-heptamethyl-3,15-dioxo-2,3,4,5,5a,6,7,7a,7b,8,9,9a,10,11,12,13,13a,15,15a,15b-icosahydro-1H-chryseno[2,1-c]azepine-12-carbonyl azide | 1297603-80-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: (5aR,7aR,7bS,9aS,12S,13aR,15aR,15bS)-5,5,7a,7b,9a,12,15b-heptamethyl-3,15-dioxo-2,3,4,5,5a,6,7,7a,7b,8,9,9a,10,11,12,13,13a,15,15a,15b-icosahydro-1H-chryseno[2,1-c]azepine-12-carbonyl azide
• CAS: 1297603-80-5
• 化学式: C₃₀H₄₄N₄O₃
• 分子量: 508.704
• InChiKey: DJVXMJMNAMWPDS-LPXJIFNVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.67
• 重原子数：
  37.0
• 可旋转键数：
  1.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  112.0
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (5aR,7aR,7bS,9aS,12S,13aR,15aR,15bS)-5,5,7a,7b,9a,12,15b-heptamethyl-3,15-dioxo-2,3,4,5,5a,6,7,7a,7b,8,9,9a,10,11,12,13,13a,15,15a,15b-icosahydro-1H-chryseno[2,1-c]azepine-12-carbonyl azide 在 氨 作用下， 以 氯仿 为溶剂， 反应 4.25h， 生成 N-[(5aR,7aR,7bS,9aS,12S,13aR,15aR,15bS)-2,3,4,5,5a,6,7,7a,7b,8,9,9a,10,11,12,13,13a,15,15a,15b-eicosahydro-5,5,7a,7b,9a,12,15b-heptamethyl-3,15-dioxo-1H-chryseno[2,1-c]azepin-12-yl]urea
  参考文献：
  名称：

  Synthesis of new glycyrrhetinic acid derived ring A azepanone, 29-urea and 29-hydroxamic acid derivatives as selective 11β-hydroxysteroid dehydrogenase 2 inhibitors

  摘要：

  Glycyrrhetinic acid, the metabolite of the natural product glycyrrhizin, is a well known nonselective inhibitor of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) type 1 and type 2. Whereas inhibition of 11 beta-HSD1 is currently under consideration for treatment of metabolic diseases, such as obesity and diabetes, 11 beta-HSD2 inhibitors may find therapeutic applications in chronic inflammatory diseases and certain forms of cancer. Recently, we published a series of hydroxamic acid derivatives of glycyrrhetinic acid showing high selectivity for 11 beta-HSD2. The most potent and selective compound is active against human 11 beta-HSD2 in the low nanomolar range with a 350-fold selectivity over human 11 beta-HSD1. Starting from the lead compounds glycyrrhetinic acid and the hydroxamic acid derivatives, novel triterpene type derivatives were synthesized and analyzed for their biological activity against overexpressed human 11 beta-HSD1 and 11 beta-HSD2 in cell lysates. Here we describe novel 29-urea- and 29-hydroxamic acid derivatives of glycyrrhetinic acid as well as derivatives with the Beckman rearrangement of the 3-oxime to a seven-membered ring, and the rearrangement of the C-ring from 11-keto-12-ene to 12-keto-9(11)-ene. The combination of modifications on different positions led to compounds comprising further improved selective inhibition of 11 beta-HSD2 in the lower nanomolar range with up to 3600-fold selectivity. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.02.005
• 作为产物：
  描述：

  3a-Aza-3,11-dioxo-A-homo-olean-12-en-30-saeure 在 氯化亚砜 、 sodium azide 作用下， 以 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 2.0h， 生成 (5aR,7aR,7bS,9aS,12S,13aR,15aR,15bS)-5,5,7a,7b,9a,12,15b-heptamethyl-3,15-dioxo-2,3,4,5,5a,6,7,7a,7b,8,9,9a,10,11,12,13,13a,15,15a,15b-icosahydro-1H-chryseno[2,1-c]azepine-12-carbonyl azide
  参考文献：
  名称：

  Synthesis of new glycyrrhetinic acid derived ring A azepanone, 29-urea and 29-hydroxamic acid derivatives as selective 11β-hydroxysteroid dehydrogenase 2 inhibitors

  摘要：

  Glycyrrhetinic acid, the metabolite of the natural product glycyrrhizin, is a well known nonselective inhibitor of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) type 1 and type 2. Whereas inhibition of 11 beta-HSD1 is currently under consideration for treatment of metabolic diseases, such as obesity and diabetes, 11 beta-HSD2 inhibitors may find therapeutic applications in chronic inflammatory diseases and certain forms of cancer. Recently, we published a series of hydroxamic acid derivatives of glycyrrhetinic acid showing high selectivity for 11 beta-HSD2. The most potent and selective compound is active against human 11 beta-HSD2 in the low nanomolar range with a 350-fold selectivity over human 11 beta-HSD1. Starting from the lead compounds glycyrrhetinic acid and the hydroxamic acid derivatives, novel triterpene type derivatives were synthesized and analyzed for their biological activity against overexpressed human 11 beta-HSD1 and 11 beta-HSD2 in cell lysates. Here we describe novel 29-urea- and 29-hydroxamic acid derivatives of glycyrrhetinic acid as well as derivatives with the Beckman rearrangement of the 3-oxime to a seven-membered ring, and the rearrangement of the C-ring from 11-keto-12-ene to 12-keto-9(11)-ene. The combination of modifications on different positions led to compounds comprising further improved selective inhibition of 11 beta-HSD2 in the lower nanomolar range with up to 3600-fold selectivity. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.02.005