(3β,18β,20β)-3-(4-hydroxy-3,3-dimethyl-1,4-dioxobutoxy)-11-oxoolean-12-en-29-oic acid

• 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)-3-(4-hydroxy-3,3-dimethyl-1,4-dioxobutoxy)-11-oxoolean-12-en-29-oic acid
• 英文别名: 2,2-dimethyl-succinic acid 4-((3S,4aR,6aR,6bS,8aS,11S,12aR,14aR,14bS)-11-carboxy-4,4,6a,6b,8a,11,14b-heptamethyl-14-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-icosahydro-picen-3-yl) ester；Butanedioic acid, 2,2-dimethyl-, 4-[(3beta)-30-hydroxy-11,30-dioxoolean-12-en-3-yl] ester；(2S,4aS,6aR,6aS,6bR,8aR,10S,12aS,14bR)-10-(3-carboxy-3-methylbutanoyl)oxy-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-3,4,5,6,6a,7,8,8a,10,11,12,14b-dodecahydro-1H-picene-2-carboxylic acid
• 化学式: C₃₆H₅₄O₇
• 分子量: 598.821
• InChiKey: KZYGGFKOMZFMNF-CNTYEJSOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  43
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  118
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2,2-二甲基琥珀酸酐 、 甘草次酸 在 吡啶 、 4-二甲氨基吡啶 作用下， 反应 12.0h， 以60%的产率得到(3β,18β,20β)-3-(4-hydroxy-3,3-dimethyl-1,4-dioxobutoxy)-11-oxoolean-12-en-29-oic acid
  参考文献：
  名称：

  Anti-AIDS Agents 69. Moronic Acid and Other Triterpene Derivatives as Novel Potent Anti-HIV Agents

  摘要：

  In a continuing structure-activity relationship study of potent anti-HIV agents, seven new triterpene derivatives were designed, synthesized, and evaluated for in vitro antiviral activity. Among them, moronic acid derivatives 19, 20, and 21 showed significant activity in HIV-1 infected H9 lymphocytes. Compounds 19 and 20 were also evaluated against HIV-1 NL4-3 and drug resistant strains in the MT-4 cell line. Compounds 19 and 20 showed better antiviral profiles than the betulinic acid analogue 8 (PA-457), which has successfully completed a Phase IIa clinical trial. Compound 20 showed potent anti-HIV activity with EC50 values of 0.0085 mu M against NL4-3, 0.021 mu M against PI-R (a multiple protease inhibitor resistant strain), and 0.13 mu M against FHR-2 (an HIV strain resistant to 8). Promising compound 20 has become a new lead for modification, and further development of 20-related compounds as clinical trial candidates is warranted.

  DOI：

  10.1021/jm0601912

文献信息

• Derivatives of 18Beta-Glycyrrhetinic Acid
  申请人：Ward Simon

  公开号：US20090076032A1

  公开（公告）日：2009-03-19

  The present invention relates to novel derivatives of 18β-glycyrrhetinic acid and methods of synthesising the derivatives. Also included within the scope of the present invention are pharmaceutical compositions comprising the derivatives of the present invention and medical uses of the derivatives, including their use in inhibiting enzymes such as retinol dehydrogenases. The present invention also relates to methods of treating diseases, such as hyperproliferative diseases, neoplasms, cancers and photoageing.

  本发明涉及18β-甘草酸的新衍生物及其合成方法。本发明的范围还包括包含本发明衍生物的制药组合物以及本发明衍生物的医学用途，包括它们在抑制酶如视黄醇脱氢酶中的使用。本发明还涉及治疗疾病的方法，例如增生性疾病、肿瘤、癌症和光老化。
• Anti-AIDS Agents 69. Moronic Acid and Other Triterpene Derivatives as Novel Potent Anti-HIV Agents
  作者：Donglei Yu、Yojiro Sakurai、Chin-Ho Chen、Fang-Rong Chang、Li Huang、Yoshiki Kashiwada、Kuo-Hsiung Lee

  DOI：10.1021/jm0601912

  日期：2006.9.1

  In a continuing structure-activity relationship study of potent anti-HIV agents, seven new triterpene derivatives were designed, synthesized, and evaluated for in vitro antiviral activity. Among them, moronic acid derivatives 19, 20, and 21 showed significant activity in HIV-1 infected H9 lymphocytes. Compounds 19 and 20 were also evaluated against HIV-1 NL4-3 and drug resistant strains in the MT-4 cell line. Compounds 19 and 20 showed better antiviral profiles than the betulinic acid analogue 8 (PA-457), which has successfully completed a Phase IIa clinical trial. Compound 20 showed potent anti-HIV activity with EC50 values of 0.0085 mu M against NL4-3, 0.021 mu M against PI-R (a multiple protease inhibitor resistant strain), and 0.13 mu M against FHR-2 (an HIV strain resistant to 8). Promising compound 20 has become a new lead for modification, and further development of 20-related compounds as clinical trial candidates is warranted.
• WO2007/105015
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis and proteasome inhibition of glycyrrhetinic acid derivatives
  作者：Li Huang、Donglei Yu、Phong Ho、Keduo Qian、Kuo-Hsiung Lee、Chin-Ho Chen

  DOI：10.1016/j.bmc.2008.05.078

  日期：2008.7

  This study discovered that glycyrrhetinic acid inhibited the human 20S proteasome at 22.3 mu M. Esterification of the C-3 hydroxyl group on glycyrrhetinic acid with various carboxylic acid reagents yielded a series of analogs with marked improved potency. Among the derivatives, glycyrrhetinic acid 3-O-isophthalate (17) was the most potent compound with IC50 of 0.22 mu M, which was approximately 100-fold more potent than glycyrrhetinic acid. (c) 2008 Elsevier Ltd. All rights reserved.
• Synthesis of glycyrrhetinic acid derivatives for the treatment of metabolic diseases
  作者：Igor Beseda、Laszlo Czollner、Priti S. Shah、Rupesh Khunt、Rawindra Gaware、Paul Kosma、Christian Stanetty、Maria Carmen del Ruiz-Ruiz、Hassan Amer、Kurt Mereiter、Thierry Da Cunha、Alex Odermatt、Dirk Claßen-Houben、Ulrich Jordis

  DOI：10.1016/j.bmc.2009.10.036

  日期：2010.1

  The effect of glycyrrhetinic acid (GA) and GA-derivatives towards 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) was investigated. Novel compounds with modi. cations at positions C-3, C-11 and C-29 of the GA skeleton were prepared. Single crystal X-ray diffraction data of selected substances are reported and discussed. (C) 2009 Elsevier Ltd. All rights reserved.