(3β)-3-hydroxy-N-methoxy-lup-20(29)-en-28-amide

• 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)-3-hydroxy-N-methoxy-lup-20(29)-en-28-amide
• 英文别名: (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-hydroxy-N-methoxy-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-carboxamide
• 化学式: C₃₁H₅₁NO₃
• 分子量: 485.751
• InChiKey: AZOBXWBDPSINGK-JVRMVBBZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8
• 重原子数：
  35
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  白桦脂酸 在 吡啶 、 4-二甲氨基吡啶 、 草酰氯 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 4.5h， 生成 (3β)-3-hydroxy-N-methoxy-lup-20(29)-en-28-amide
  参考文献：
  名称：

  Triterpenoid Hydroxamates as HIF Prolyl Hydrolase Inhibitors

  摘要：

  Pentacyclic triterpenoid acids (PCTTAs) are pleiotropic agents that target many macromolecular endpoints with low to moderate affinity. To explore the biological space associated with PCTTAs, we have investigated the carboxylate-to-hydroxamate transformation, discovering that it de-emphasizes affinity for the transcription factors targeted by the natural compounds (NF-kappa B, STAT3, Nrf2, TGRS) and selectively induces inhibitory activity on HIF prolyl hydrolases (PHDs). Activity was reversible, isoform-selective, dependent on the hydroxamate location, and negligible when this group was replaced by other chelating elements or O-alkylated. The hydroxamate of betulinic acid (Sb) was selected for further studies, and evaluation of its effect on HIF-la expression under normal and hypoxic conditions qualified it as a promising lead structure for the discovery of new candidates in the realm of neuroprotection.

  DOI：

  10.1021/acs.jnatprod.8b00514

文献信息

• Betulinic acid derived hydroxamates and betulin derived carbamates are interesting scaffolds for the synthesis of novel cytotoxic compounds
  作者：Jana Wiemann、Lucie Heller、Vincent Perl、Ralph Kluge、Dieter Ströhl、René Csuk

  DOI：10.1016/j.ejmech.2015.10.043

  日期：2015.12

  The betulinic acid-derived hydroxamates 5-18, the amides 19-24, and betulin-derived bis-carbamates 25-28 as well as the carbamates 31-40 and 44-48 were prepared and evaluated for their anti-proliferative activity in a photometric sulforhodamine B (SRB) assay against several human cancer cell lines and nonmalignant mouse fibroblasts (NIH 3T3). While for 3-O-acetyl hydroxamic acid 5 EC50 values as low as EC50 = 1.3 mu M were found, N,O-bis-alkyl substituted hydroxamates showed lowered cytotoxicity (EC50 = 16-20 mu M). In general, hydroxamic acid derivatives showed only reduced selectivity for tumor cells, except for allyl substituted compound 13 (EC50 = 5.9 mu M for A2780 human ovarian carcinoma cells and EC50 > 30 mu M for nonmalignant mouse fibroblasts). The cytotoxicity of betulinic acid derived amides 19-24 and of betulin derived bis-carbamates 25-28 was low, except for N-ethyl substituted 25. Hexyl substituted 39 showed EC50 = 5.6 mu M (518A2 cells) while for mouse fibroblasts EC50 > 30 was determined. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Triterpenoid Hydroxamates as HIF Prolyl Hydrolase Inhibitors
  作者：Alberto Minassi、Federica Rogati、Cristina Cruz、M. Eugenia Prados、Nuria Galera、Carla Jinénez、Giovanni Appendino、M. Luz Bellido、Marco A Calzado、Diego Caprioglio、Eduardo Muñoz

  DOI：10.1021/acs.jnatprod.8b00514

  日期：2018.10.26

  Pentacyclic triterpenoid acids (PCTTAs) are pleiotropic agents that target many macromolecular endpoints with low to moderate affinity. To explore the biological space associated with PCTTAs, we have investigated the carboxylate-to-hydroxamate transformation, discovering that it de-emphasizes affinity for the transcription factors targeted by the natural compounds (NF-kappa B, STAT3, Nrf2, TGRS) and selectively induces inhibitory activity on HIF prolyl hydrolases (PHDs). Activity was reversible, isoform-selective, dependent on the hydroxamate location, and negligible when this group was replaced by other chelating elements or O-alkylated. The hydroxamate of betulinic acid (Sb) was selected for further studies, and evaluation of its effect on HIF-la expression under normal and hypoxic conditions qualified it as a promising lead structure for the discovery of new candidates in the realm of neuroprotection.