3-O-acetyl-23-acetoxy-N-(2-aminoethyl)betulinic amide | 1215746-46-5

• 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: 3-O-acetyl-23-acetoxy-N-(2-aminoethyl)betulinic amide
• 英文别名: 3,23-diacetoxybetulinic 2-aminoethyl amide；[(1R,3aS,5aR,5bR,7aR,8R,9S,11aR,11bR,13aR,13bR)-9-acetyloxy-3a-(2-aminoethylcarbamoyl)-5a,5b,8,11a-tetramethyl-1-prop-1-en-2-yl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysen-8-yl]methyl acetate
• CAS: 1215746-46-5
• 化学式: C₃₆H₅₈N₂O₅
• 分子量: 598.867
• InChiKey: OBLQKZJTZKUVKP-IFDXBLLESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  43
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-O-acetyl-23-acetoxy-N-(2-aminoethyl)betulinic amide 在 水 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 以94%的产率得到23-hydroxy-N-(2-aminoethyl)betulinic amide
  参考文献：
  名称：

  [EN] TRITERPENOID COMPOUNDS AND METHODS OF USE THEREOF
  [FR] COMPOSÉS TRITERPÉNOÏDES ET PROCÉDÉS POUR LES UTILISER

  摘要：

  本发明提供了作为受体拮抗剂的治疗活性化合物和组合物，以及它们的使用方法。在一个方面，这些化合物在通过抑制包括PGE2 EP1、EP2和EP4受体在内的PGE2受体来调节疼痛、炎症和急性阶段反应方面是有用的。

  公开号：

  WO2010032123A1
• 作为产物：
  描述：

  23-hydroxybetulinic acid 在 吡啶 、 草酰氯 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 3-O-acetyl-23-acetoxy-N-(2-aminoethyl)betulinic amide
  参考文献：
  名称：

  Synthesis and antiproliferative evaluation of 23-hydroxybetulinic acid derivatives

  摘要：

  Based on structural modifications of the natural 23-hydroxybetulinic acid, a series of novel its derivatives had been synthesized. The new compounds were screened for in vitro antiproliferative activity against cancer cell lines HeLa, MCF-7, HepG2. B16 and A375 using doxorubicin as a reference. The vast majority of derivatives had exhibited potent tumor growth inhibitory activity than original compound. The derivatives 4, 5, 7, 20, 23, 26, 43 and 44 with IC50 values lower than 10 mu M on all tested cell lines were regarded as the most promising compounds. The structure activity relationships of 23-hydroxybetulinic acid derivatives were also discussed in the present investigations. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.03.038

文献信息

• Design and synthesis of NAD(P)H: Quinone oxidoreductase (NQO1)-activated prodrugs of 23-hydroxybetulinic acid with enhanced antitumor properties
  作者：Huajian Zhu、Lixue Lu、Wenjian Zhu、Yuchen Tan、Yiping Duan、Jie Liu、Wencai Ye、Zheying Zhu、Jinyi Xu、Shengtao Xu

  DOI：10.1016/j.ejmech.2022.114575

  日期：2022.10

  those of parent compound 23-HBA. More importantly, it was demonstrated in the in vivo antitumor experiment that 32j effectively suppressed the tumor volume and largely reduced tumor weight by 72.69% with no apparent toxicity, which was more potent than the positive control 5-fluorouracil. This is the first breakthrough in the improvement of in vivo antitumor activities of 23-HBA derivatives. The further

  通过将吲哚醌部分引入23-羟基桦木酸（23-HBA）及其类似物的C-3、C-23或C-28位，设计合成了一系列NQO1选择性活化前药。其中，代表化合物32j对 NQO1 过表达的 HT-29 细胞和 A549 细胞具有显着的抗增殖活性，IC 50值分别为 1.87 和 2.36 μM，是母体化合物 23 的 20-30 倍-HBA。更重要的是，体内抗肿瘤实验证明32j有效抑制肿瘤体积，肿瘤重量大幅减少72.69%，无明显毒性，比阳性对照5-氟尿嘧啶更有效。这是提高23-HBA衍生物体内抗肿瘤活性的第一个突破。进一步的分子机制研究表明，32j在 G2/M 期阻断细胞周期停滞、诱导细胞凋亡、去极化线粒体并以剂量依赖性方式提高细胞内 ROS 水平。Western印迹分析表明，32j通过干扰细胞凋亡相关蛋白的表达诱导细胞凋亡。这些发现表明化合物32j可以被认为是一种有效的抗肿瘤前药候选物，值得进一步研究用于个体化癌症治疗。
• [EN] TRITERPENOID COMPOUNDS AND METHODS OF USE THEREOF<br/>[FR] COMPOSÉS TRITERPÉNOÏDES ET PROCÉDÉS POUR LES UTILISER
  申请人：BIOTECHNOLOGY RES CORP LTD

  公开号：WO2010032123A1

  公开（公告）日：2010-03-25

  The present invention provides therapeutically active compounds and compositions as receptor antagonists and methods of use thereof. In one aspect, the compounds are useful in modulating pain, inflammation and acute phase reactions by inhibiting the PGE2 receptors including PGE2 EP1, EP2 and EP4 receptors.

  本发明提供了作为受体拮抗剂的治疗活性化合物和组合物，以及它们的使用方法。在一个方面，这些化合物在通过抑制包括PGE2 EP1、EP2和EP4受体在内的PGE2受体来调节疼痛、炎症和急性阶段反应方面是有用的。
• Synthesis and antiproliferative evaluation of 23-hydroxybetulinic acid derivatives
  作者：Ping Lan、Jiao Wang、Dong-Mei Zhang、Chang Shu、Hui-Hui Cao、Ping-Hua Sun、Xiao-Ming Wu、Wen-Cai Ye、Wei-Min Chen

  DOI：10.1016/j.ejmech.2011.03.038

  日期：2011.6

  Based on structural modifications of the natural 23-hydroxybetulinic acid, a series of novel its derivatives had been synthesized. The new compounds were screened for in vitro antiproliferative activity against cancer cell lines HeLa, MCF-7, HepG2. B16 and A375 using doxorubicin as a reference. The vast majority of derivatives had exhibited potent tumor growth inhibitory activity than original compound. The derivatives 4, 5, 7, 20, 23, 26, 43 and 44 with IC50 values lower than 10 mu M on all tested cell lines were regarded as the most promising compounds. The structure activity relationships of 23-hydroxybetulinic acid derivatives were also discussed in the present investigations. (C) 2011 Elsevier Masson SAS. All rights reserved.