3β-[(4-carboxyl-3,3-dimethyl)butyryloxy]-urs-12-en-28-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-[(4-carboxyl-3,3-dimethyl)butyryloxy]-urs-12-en-28-oic acid
• 英文别名: 3-O-(3',3'-Dimethylglutaryl)-ursolic acid；(1S,2R,4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-10-(4-carboxy-3,3-dimethylbutanoyl)oxy-1,2,6a,6b,9,9,12a-heptamethyl-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene-4a-carboxylic acid
• 化学式: C₃₇H₅₈O₆
• 分子量: 598.864
• InChiKey: KVCMCAKBAUHBEG-NFSMWPDXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.5
• 重原子数：
  43
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  熊果酸 在 吡啶 、 4-二甲氨基吡啶 、 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 生成 3β-[(4-carboxyl-3,3-dimethyl)butyryloxy]-urs-12-en-28-oic acid
  参考文献：
  名称：

  Synthesis, biological evaluation and SAR studies of ursolic acid 3β-ester derivatives as novel CETP inhibitors

  摘要：

  Cholesteryl ester transfer protein (CETP) is an attractive therapeutic target for the prevention and treatment of cardiovascular diseases by lowering low-density lipoprotein cholesterol levels as well as raising high-density lipoprotein cholesterol levels in human plasma. Herein, a series of ursolic acid 3 beta-ester derivatives were designed, synthesized and evaluated for the CETP inhibiting activities. Among these compounds, the most active compound is U12 with an IC50 value of 2.4 mu M in enzymatic assay. The docking studies showed that the possible hydrogen bond interactions between the carboxyl groups at both ends of the molecule skeleton and several polar residues (such as Ser191, Cys13 and Ser230) in the active site region of CETP could significantly enhance the inhibition activity. This study provides structural insight of the interactions between these pentacyclic tri-terpenoid 3 beta-ester derivatives and CETP protein for the further modification and optimization.

  DOI：

  10.1016/j.bmcl.2019.126824

文献信息

• Anti-AIDS Agents 38. Anti-HIV Activity of 3-<i>O</i>-Acyl Ursolic Acid Derivatives
  作者：Yoshiki Kashiwada、Tsuneatsu Nagao、Ayumi Hashimoto、Yasumasa Ikeshiro、Hikaru Okabe、L. Mark Cosentino、Kuo-Hsiung Lee

  DOI：10.1021/np990633v

  日期：2000.12.1

  Based on our previous finding that 3-O-acyl-betulinic and -oleanolic acids, especially the 3-O-(3',3'-dimethyl)-succinyl derivatives (2 and 4), demonstrated potent anti-HIV activity [EC50 < 0.00035 and 0.00086 M; therapeutic index (TI) > 20 000 and 22 326, respectively], several 3-O-acyl-ursolic acids were prepared and evaluated for anti-HIV activity. Ursolic acid (6) was equipotent (EC50 4.4 muM) with oleanolic acid (EC50 3.7 muM), although it was slightly toxic (IC50 14.3 CIM, TI 3.3). 3-O-Diglycoryl-ursolic acid (10) demonstrated relatively potent anti-HIV activity with an EC50 of 0.31 muM and a TI of 155.5. In contrast, 3-O-(3',3'-dimethylsuccinyl)-ursolic acid (8), which is analogous to the extremely potent anti-HIV betulinic acid and oleanolic acid derivatives 2 and 4, displayed only weak anti-HIV activity (EC50 2.1 muM, TI 23.6).