3β-benzoyloxy-lup-20(29)-en-28-oic acid | 75365-43-4

• 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-benzoyloxy-lup-20(29)-en-28-oic acid
• 英文别名: 3β-benzoylbetulinic acid；(1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-(benzoyloxy)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysene-3a-carboxylic acid；3β-benzoyloxy-lupen-(20(29))-oic acid-(28)；3β-Benzoyloxy-lupen-(20(29))-saeure-(28)；Betulinic acid 3-O-benzoate；(1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-benzoyloxy-5a,5b,8,8,11a-pentamethyl-1-prop-1-en-2-yl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysene-3a-carboxylic acid
• CAS: 75365-43-4
• 化学式: C₃₇H₅₂O₄
• 分子量: 560.817
• InChiKey: NLNQDRBZXLUPQC-DWKDZXJCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.4
• 重原子数：
  41
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  重氮甲烷 、 3β-benzoyloxy-lup-20(29)-en-28-oic acid 生成 3β-benzoyloxy-lupen-(20(29))-oic acid-(28)-methyl ester
  参考文献：
  名称：

  Kawaguchi; Kim, Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1940, vol. 60, p. 343,348; dtsch. Ref. S. 171

  摘要：

  DOI：
• 作为产物：
  描述：

  白桦脂醇-3-乙酸酯 在 吡啶 、 chromium(VI) oxide 、 氢氧化钾 、 溶剂黄146 作用下， 生成 3β-benzoyloxy-lup-20(29)-en-28-oic acid
  参考文献：
  名称：

  Kawaguchi; Kim, Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1940, vol. 60, p. 343,348; dtsch. Ref. S. 171

  摘要：

  DOI：

文献信息

• New betulinic acid derivatives as potent proteasome inhibitors
  作者：Keduo Qian、Sang-Yong Kim、Hsin-Yi Hung、Li Huang、Chin-Ho Chen、Kuo-Hsiung Lee

  DOI：10.1016/j.bmcl.2011.07.072

  日期：2011.10

  study, 22 new betulinic acid (BA) derivatives were synthesized and tested for their inhibition of the chymotrypsin-like activity of 20S proteasome. From the SAR study, we concluded that the C-3 and C-30 positions are the pharmacophores for increasing the proteasome inhibition effects, and larger lipophilic or aromatic side chains are favored at these positions. Among the BA derivatives tested, compounds

  在这项研究中，合成了 22 种新的桦木酸 (BA) 衍生物并测试了它们对 20S 蛋白酶体的胰凝乳蛋白酶样活性的抑制作用。从 SAR 研究中，我们得出结论，C-3 和 C-30 位置是增加蛋白酶体抑制作用的药效团，并且在这些位置有利于较大的亲脂或芳香侧链。在测试的BA衍生物，化合物13，20，和21显示出最好的蛋白酶体抑制活性，IC 50个分别1.42，1.56，和1.80μM，的值，它是三至四倍比蛋白酶体抑制控制LLM-F更有效和乳胱氨酸。
• Application of a fluorine strategy in the lead optimization of betulinic acid to the discovery of potent CD73 inhibitors
  作者：Yanming Zhang、Keli Yang、Shuang Ye、Wenmin Tang、Xuliang Chang、Yuan Wang、Chuanhao Wang、Ying Wang、Yuelin Wu、Zhenyuan Miao

  DOI：10.1016/j.steroids.2022.109112

  日期：2022.12

  The ecto-5'-nucleotidase (CD73) is an important enzyme in the adenosine pathway and catalyzes the extracellular hydrolysis of adenosine monophosphate (AMP) yielding adenosine which is involved in the inflammation and immunosuppression. Inhibitors of CD73 have potential as novel immunotherapy agents for the treatment of cancer and infection. In this study, we discovered a series of fluorinated betulinic acid derivatives as potent CD73 inhibitors by a fluorine scanning strategy. Among these, three compounds ZM522, ZM553 and ZM557 exhibited inhibitory activity with IC50 values of 0.56 uM, 0.74 uM and 0.47 uM, respectively. In addition, these compounds showed a 7-fold, 5-fold and 8-fold increase in activity compared to the positive control drug α, β-methylene adenosine diphosphate (APCP) against the human CD73 enzyme. Two of these (ZM522 and ZM553) also exhibited effective interferon gamma (INF-γ) elevation and indicated the regulation of rescued T cell activation. Therefore, our study provides both a lead optimization strategy and potential compounds for further development of small molecule CD73 inhibitors.
• Design, synthesis and biological evaluation of betulinic acid derivatives as potential inhibitors of 3CL-protease of SARS-CoV-2
  作者：Yaowen Liu、Tianqing Nie、Jinjun Hou、Huali Long、Zijia Zhang、Min Lei、Yechun Xu、Wanying Wu

  DOI：10.1016/j.steroids.2023.109351

  日期：2024.2