N-(3-β-acetoxy-ursane-12-ene-28-acyl)-aniline | 929076-64-2

• 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-(3-β-acetoxy-ursane-12-ene-28-acyl)-aniline
• 英文别名: [(3S,4aR,6aR,6bS,8aS,11R,12S,12aS,14aR,14bR)-4,4,6a,6b,11,12,14b-heptamethyl-8a-(phenylcarbamoyl)-2,3,4a,5,6,7,8,9,10,11,12,12a,14,14a-tetradecahydro-1H-picen-3-yl] acetate
• CAS: 929076-64-2
• 化学式: C₃₈H₅₅NO₃
• 分子量: 573.86
• InChiKey: CINHTIKOIXDBSB-MKXNTKMZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.2
• 重原子数：
  42
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  熊果酸乙酸酯 在 草酰氯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 42.0h， 生成 N-(3-β-acetoxy-ursane-12-ene-28-acyl)-aniline
  参考文献：
  名称：

  In vitro and in vivo evaluation of the antidiabetic activity of ursolic acid derivatives

  摘要：

  In this study, a series of ursolic acid derivatives were synthesized, and their structures were confirmed. The activity of the synthesized compounds against α-glucosidase was determined in vitro. The results suggested that all compounds have significant inhibitory activity, especially compounds 3-5 and 8, the IC50 values of which were 2.66 ± 0.84, 1.01 ± 0.44, 3.26 ± 0.22, and 3.24 ± 0.21 μM. These compounds were more potent than acarbose (positive control) against α-glucosidase. Kinetic studies were performed to determine the mechanism of inhibition by compounds 3-5 and 8. The kinetic inhibition studies indicated that compound 3 was a non-competitive inhibitor, and the inhibition constant Ki was calculated to be 2.67 ± 0.19 μM. Moreover, the kinetic inhibition studies of compounds 4, 5 and 8 demonstrated that they were mixed-type inhibitors. Furthermore, the actual pharmacological potentials of synthesized compounds 3 and 4 were demonstrated by the reduction of postprandial blood glucose levels in normal Kunming mice. The hypoglycemic effects of these compounds were more evident 30 and 60 min after maltose ingestion (P < 0.05), which was similar to the effect displayed by the positive control, acarbose.

  DOI：

  10.1016/j.ejmech.2014.04.073

文献信息

• 乌苏酸化学修饰物及其制备方法和应用
  申请人：广东工业大学

  公开号：CN104045678B

  公开（公告）日：2016-03-02

  本发明公开了一种乌苏酸化学修饰物及其制备方法和应用，该乌苏酸化学修饰物结构式为下式：其中：R1为酰基；R2为胺基：制备方法，乌苏酸和酸酐在催化剂条件下反应得到3β‐酰氧基‐乌苏烷型‐12‐烯‐28‐羧酸类化合物2～5；化合物2～5利用草酰氯在冰浴条件下酰化，得到3‐乙酰氧基‐乌苏烷型‐12烯‐28‐酰氯，再在缚酸剂条件下，与苯胺反应得N‐(3β‐乙酰氧基‐乌苏烷型‐12‐烯‐28‐酰)‐胺类化合物；该化合物具有抑制酶活性的作用，可应用在制备预防、控制或治疗血糖水平升高糖尿病或肥胖症的药品、饮品、食品和保健品中；属于药物合成技术领域。
• Side chain-functionalized aniline-derived ursolic acid derivatives as multidrug resistance reversers that block the nuclear factor-kappa B (NF-κB) pathway and cell proliferation
  作者：Ri-Zhen Huang、Shi-Xian Hua、Zhi-Xin Liao、Xiao-Chao Huang、Heng-Shan Wang

  DOI：10.1039/c7md00105c

  日期：——

  A series of inhibitors of NF-κB based on ursolic acid (UA) derivatives containing functionalized aniline or amide side chains were synthesized and evaluated for inhibition of NF-κB as well as their antitumor effects. These compounds exhibited significant inhibition activity toward NF-κB with IC50 values at micromolar concentrations in the NCI-H460 lung adenocarcinoma cell line. A docking study of the

  合成了一系列基于熊果酸（UA）衍生物的NF-κB抑制剂，这些衍生物含有官能化的苯胺或酰胺侧链，并评估了其对NF-κB的抑制作用及其抗肿瘤作用。这些化合物在微摩尔浓度的NCI-H460肺腺癌细胞系中对NF-κB表现出明显的抑制活性，IC 50值为50。对活性最高的化合物5Y8的对接研究显示，5Y8与NF-κB活性位点之间的关键相互作用，其中C-28位的官能化酰胺部分和C-3位的酯基对于提高活性很重要。特别是化合物5Y8似乎是对NCI-H460细胞系最有效的化合物，并且至少部分地通过阻断NF-κB信号通路并诱导凋亡，在药物敏感性和耐药性癌细胞系中显示出相似的效率。从机制上讲，化合物5Y8可能会触发凋亡信号通路。因此，具有功能化苯胺或酰胺侧链的UA衍生物的合理设计为发现具有诱导NCI-H460肺腺癌细胞凋亡和逆转多药耐药性的新型NF-κB抑制剂提供了巨大的潜力。