N-hydroxy-N-methyl-N'-[(3β,18β,20β)-3-(acetoxy)-11-oxo-30-norolean-12-en-20-yl]urea | 1297603-98-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: N-hydroxy-N-methyl-N'-[(3β,18β,20β)-3-(acetoxy)-11-oxo-30-norolean-12-en-20-yl]urea
• 英文别名: N-hydroxy-N-methyl-N'-[(3β,18β,20β)-3-(acetyloxy)-11-oxo-30-norolean-12-en-20-yl]urea；[(3S,4aR,6aR,6bS,8aS,11S,12aR,14aR,14bS)-11-[[hydroxy(methyl)carbamoyl]amino]-4,4,6a,6b,8a,11,14b-heptamethyl-14-oxo-2,3,4a,5,6,7,8,9,10,12,12a,14a-dodecahydro-1H-picen-3-yl] acetate
• CAS: 1297603-98-5
• 化学式: C₃₃H₅₂N₂O₅
• 分子量: 556.786
• InChiKey: GPKAARJXPCYEQP-IREBYWSLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  40
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  95.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  甘草次酸 在 sodium azide 、 碳酸氢钠 作用下， 以 四氢呋喃 、 氯仿 、 丙酮 为溶剂， 反应 15.5h， 生成 N-hydroxy-N-methyl-N'-[(3β,18β,20β)-3-(acetoxy)-11-oxo-30-norolean-12-en-20-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

文献信息

• [EN] GLYCYRRHETINIC ACID AMINE ANALOGUES FOR USE IN THE TREATMENT OF INFLAMMATION, INFECTIOUS DISEASES, CANCER, AUTOIMMUNE DISEASES, SKIN DISEASES, BONE DISEASES AND METABOLIC DISEASES<br/>[FR] ANALOGUES AMINE D'ACIDE GLYCYRRHÉTINIQUE DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT DE L'INFLAMMATION, DES MALADIES INFECTIEUSES, DU CANCER, DES MALADIES AUTO-IMMUNES, DES MALADIES DE LA PEAU, DES MALADIES DES OS ET DES MALADIES MÉTABOLIQUES
  申请人：ONEPHARM RES & DEV GMBH

  公开号：WO2012020021A9

  公开（公告）日：2012-05-10
• 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.