N-[(3β,18β,20β)-[3-(1,2,4-oxadiazole-5(2H)-one-3-oxy)]-11-oxo-30-norolean-12-en-20-yl]urea | 1297603-75-8

• 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-[(3β,18β,20β)-[3-(1,2,4-oxadiazole-5(2H)-one-3-oxy)]-11-oxo-30-norolean-12-en-20-yl]urea
• 英文别名: 1-((2S,4aS,6aS,6bR,8aR,10S,12aS,12bR,14bR)-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-10-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yloxy)-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicen-2-yl)urea；[(2S,4aS,6aR,6aS,6bR,8aR,10S,12aS,14bR)-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-10-[(5-oxo-4H-1,2,4-oxadiazol-3-yl)oxy]-3,4,5,6,6a,7,8,8a,10,11,12,14b-dodecahydro-1H-picen-2-yl]urea
• CAS: 1297603-75-8
• 化学式: C₃₂H₄₈N₄O₅
• 分子量: 568.757
• InChiKey: HOKWINYUFDACLI-UOEOWSRYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  41
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  132
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  甘草次酸 在 sodium azide 、 盐酸羟胺 、 氨 、 potassium hydroxide 、 lithium hydroxide 作用下， 以 甲醇 、 乙醇 、 氯仿 、 丙酮 为溶剂， 反应 108.0h， 生成 N-[(3β,18β,20β)-[3-(1,2,4-oxadiazole-5(2H)-one-3-oxy)]-11-oxo-30-norolean-12-en-20-yl]urea
  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.
• [EN] NOVEL TRITERPENE DERIVATIVES<br/>[FR] NOUVEAUX DÉRIVÉS TRITERPÉNIQUES
  申请人：ONEPHARM RES & DEV GMBH

  公开号：WO2012020019A1

  公开（公告）日：2012-02-16

  The present invention encompasses compounds of general formula (I) wherein R11a to R30 and X are defined as in claim 1, which are suitable for the treatment of and/or prevention of chronic inflammatory diseases, autoimmune diseases, skin diseases, bone diseases, metabolic diseases, infectious diseases and cancer.

  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。