28-(4-methylpiperazin-1-yl)-28-oxours-12-en-3β-yl acetate

• 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: 28-(4-methylpiperazin-1-yl)-28-oxours-12-en-3β-yl acetate
• 英文别名: [(3S,4aR,6aR,6bS,8aS,11R,12S,12aS,14aR,14bR)-4,4,6a,6b,11,12,14b-heptamethyl-8a-(4-methylpiperazine-1-carbonyl)-2,3,4a,5,6,7,8,9,10,11,12,12a,14,14a-tetradecahydro-1H-picen-3-yl] acetate
• 化学式: C₃₇H₆₀N₂O₃
• 分子量: 580.895
• InChiKey: HAQIVXVGIDTAII-CVTBAMPXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  42
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  28-(4-methylpiperazin-1-yl)-28-oxours-12-en-3β-yl acetate 在 双氧水 作用下， 以 甲醇 、 水 为溶剂， 反应 48.0h， 以96%的产率得到28-(4-methyl-4-oxidopiperazin-1-yl)-28-oxours-12-en-3β-yl acetate
  参考文献：
  名称：

  The presence of a cationic center is not alone decisive for the cytotoxicity of triterpene carboxylic acid amides

  摘要：

  3-O-Acetyl-ursolic acid (2) and 3-O-acetyl oleanolic acid (8) were converted into piperazinylamides holding a distal NH, NMe or a NMe2 group. These compounds as well as the corresponding N-methyl-N-oxides were accessed. Their cytotoxicity was assessed in SRB assays employing a panel of human tumor cell lines and non-malignant fibroblasts (NIH 3T3). As a result, compounds holding a quaternary distal N-substituent were less cytotoxic that those holding a NH-moiety. Hence, the presence of a distal cationic center seems not to be a sufficient criterion for obtaining triterpenoids of high cytotoxicity and selectivity.

  DOI：

  10.1016/j.steroids.2020.108713
• 作为产物：
  描述：

  熊果酸 在 4-二甲氨基吡啶 、 草酰氯 作用下， 以 吡啶 、 二氯甲烷 为溶剂， 反应 10.0h， 生成 28-(4-methylpiperazin-1-yl)-28-oxours-12-en-3β-yl acetate
  参考文献：
  名称：

  侧链官能化的苯胺衍生的乌索酸衍生物作为多药抗性逆转剂，可阻断核因子-κB（NF-κB）途径和细胞增殖

  摘要：

  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。

  DOI：

  10.1039/c7md00105c

文献信息

• 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。
• The presence of a cationic center is not alone decisive for the cytotoxicity of triterpene carboxylic acid amides
  作者：Benjamin Brandes、Lukas Koch、Sophie Hoenke、Hans-Peter Deigner、René Csuk

  DOI：10.1016/j.steroids.2020.108713

  日期：2020.11

  3-O-Acetyl-ursolic acid (2) and 3-O-acetyl oleanolic acid (8) were converted into piperazinylamides holding a distal NH, NMe or a NMe2 group. These compounds as well as the corresponding N-methyl-N-oxides were accessed. Their cytotoxicity was assessed in SRB assays employing a panel of human tumor cell lines and non-malignant fibroblasts (NIH 3T3). As a result, compounds holding a quaternary distal N-substituent were less cytotoxic that those holding a NH-moiety. Hence, the presence of a distal cationic center seems not to be a sufficient criterion for obtaining triterpenoids of high cytotoxicity and selectivity.