(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-N-hydroxy-N-methyl-1H-chryseno[2,1-c]azepine-12-carboxylic acid amid | 1297603-96-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (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-N-hydroxy-N-methyl-1H-chryseno[2,1-c]azepine-12-carboxylic acid amid
• 英文别名: (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-N-hydroxy-N-methyl-1H-chryseno[2,1-c]azepine-12-carboxylic acid amide；(1R,2S,5S,8S,10R,14R,15S,21R)-N-hydroxy-N,1,2,5,8,15,20,20-octamethyl-13,18-dioxo-19-azapentacyclo[12.9.0.02,11.05,10.015,21]tricos-11-ene-8-carboxamide
• CAS: 1297603-96-3
• 化学式: C₃₁H₄₈N₂O₄
• 分子量: 512.733
• InChiKey: AUQXBLHDEASREV-GJIZTULQSA-N

物化性质

• 密度：
  1.16±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  37
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  86.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  甘草次酸 在 palladium 10% on activated carbon 吡啶 、 氯化亚砜 、 五氯化磷 、 盐酸羟胺 、 氢气 、 三乙胺 、 pyridinium chlorochromate 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 为溶剂， 20.0~50.0 ℃ 、200.0 kPa 条件下， 反应 45.5h， 生成 (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-N-hydroxy-N-methyl-1H-chryseno[2,1-c]azepine-12-carboxylic acid amid
  参考文献：
  名称：

  [EN] NOVEL TRITERPENE DERIVATIVES
  [FR] NOUVEAUX DÉRIVÉS TRITERPÉNIQUES

  摘要：

  本发明涵盖了一般式（I）中R11a到R30和X的化合物，其中如权利要求书中所定义的，适用于治疗和/或预防慢性炎症性疾病、自身免疫疾病、皮肤疾病、骨疾病、代谢性疾病、传染病和癌症。

  公开号：

  WO2012020019A1

文献信息

• Synthesis of new glycyrrhetinic acid derived ring A azepanone, 29-urea and 29-hydroxamic acid derivatives as selective 11β-hydroxysteroid dehydrogenase 2 inhibitors
  作者：Rawindra Gaware、Rupesh Khunt、Laszlo Czollner、Christian Stanetty、Thierry Da Cunha、Denise V. Kratschmar、Alex Odermatt、Paul Kosma、Ulrich Jordis、Dirk Claßen-Houben

  DOI：10.1016/j.bmc.2011.02.005

  日期：2011.3

  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.