(3β,18β,20β)-N-[-3-(acetoxy)-11-oxo-30-norolean-12-en-20-yl]urea | 1297603-97-4

• 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: (3β,18β,20β)-N-[-3-(acetoxy)-11-oxo-30-norolean-12-en-20-yl]urea
• 英文别名: 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-(carbamoylamino)-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: 1297603-97-4
• 化学式: C₃₂H₅₀N₂O₄
• 分子量: 526.76
• InChiKey: WBHDMKZEFCLSRV-XWEVEMRCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  38
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  98.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3β,18β,20β)-N-[-3-(acetoxy)-11-oxo-30-norolean-12-en-20-yl]urea 在 盐酸羟胺 、 potassium hydroxide 、 lithium hydroxide 作用下， 以 甲醇 、 乙醇 、 氯仿 为溶剂， 反应 106.25h， 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
• 作为产物：
  描述：

  甘草次酸 在 吡啶 、 氯化亚砜 、 sodium azide 、 氨 作用下， 以 四氢呋喃 、 氯仿 、 水 、 乙酸乙酯 为溶剂， 反应 14.0h， 生成 (3β,18β,20β)-N-[-3-(acetoxy)-11-oxo-30-norolean-12-en-20-yl]urea
  参考文献：
  名称：

  新型甘草甜素脲类抗炎药治疗急性肾损伤的设计与合成

  摘要：

  为了开发用于预防和治疗急性肾损伤的新型抗炎药，使用 RAW264.7 细胞设计、合成和评估了一系列新型甘草酸尿素的抗炎活性。具有酸性或中性氨基酸的化合物5r-5u（分别为 2.04、2.50、3.25 和 2.48 μM）显示出有效的抗炎活性（ 对于 NO 抑制，IC 50 = 2-3 μM），其中，化合物5r还抑制肿瘤坏死因子-α (TNF-α) 和白细胞介素-6 (IL-6) 呈剂量依赖性。在顺铂诱导的 AKI 小鼠模型中，化合物5r显着降低促炎因子水平，改善肾脏组织病理损伤，维持正常代谢能力。

  DOI：

  10.1016/j.bioorg.2021.104755

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] 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
• METHODS AND COMPOSITIONS FOR TREATING ALCOHOL USE DISORDERS
  申请人：SANNA Pietro Paolo

  公开号：US20170232007A1

  公开（公告）日：2017-08-17

  Disclosed are methods and compositions for treating alcohol dependence by administration to a patient of an inhibitor of 11β-hydroxysteroid dehydrogenases (11β-HSD) to modulate glucocorticoid effects. One such compound is the 11β-HSD inhibitor carbenoxolone (18β-glycyrrhetinic acid 3β-O-hemisuccinate), which has been extensively employed in the clinic for the treatment of gastritis and peptic ulcer. Carbenoxolone is active on both 11β-HSD1 and 2 isoforms. Here, carbenoxolone is surprisingly shown to reduce both baseline and excessive drinking in rats and mice. The carbenoxolone diastereomer 18α-glycyrrhetinic acid 3β-O-hemisuccinate (αCBX), which the applicants discovered to be selective for 11β-HSD2, was also effective in reducing alcohol drinking in mice. Thus, 11β-HSD inhibitors are a new class of candidate alcohol abuse medications and existing 11β-HSD inhibitor drugs may be re-purposed for alcohol abuse treatment.
• [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。
• Design and synthesis of novel glycyrrhetin ureas as anti-inflammatory agents for the treatment of acute kidney injury
  作者：Hongbo Wang、Jiawei Zuo、Liang Zha、Xia Jiang、Caixia Wu、Yong-An Yang、Wenjian Tang、Tianlu Shi

  DOI：10.1016/j.bioorg.2021.104755

  日期：2021.5

  To develop new anti-inflammatory drugs for the prevention and treatment of acute kidney injury, a series of novel glycyrrhetic ureas were designed, synthesized and evaluated for anti-inflammatory activity using RAW264.7 cells. Compounds 5r-5u (2.04, 2.50, 3.25 and 2.48 μM, respectively) with acidic or neutral amino acid showed potent anti-inflammatory activity (IC50 = 2–3 μM for NO inhibition), amongst

  为了开发用于预防和治疗急性肾损伤的新型抗炎药，使用 RAW264.7 细胞设计、合成和评估了一系列新型甘草酸尿素的抗炎活性。具有酸性或中性氨基酸的化合物5r-5u（分别为 2.04、2.50、3.25 和 2.48 μM）显示出有效的抗炎活性（ 对于 NO 抑制，IC 50 = 2-3 μM），其中，化合物5r还抑制肿瘤坏死因子-α (TNF-α) 和白细胞介素-6 (IL-6) 呈剂量依赖性。在顺铂诱导的 AKI 小鼠模型中，化合物5r显着降低促炎因子水平，改善肾脏组织病理损伤，维持正常代谢能力。