3,11-dioxo-2-trifluoroacetyl-olean-12-en-30-oic acid methyl ester | 184848-75-7

• 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: 3,11-dioxo-2-trifluoroacetyl-olean-12-en-30-oic acid methyl ester
• 英文别名: methyl (2S,4aS,6aS,6bR,8aR,12aS,12bR,14bR)-2,4a,6a,6b,9,9,12a-heptamethyl-10,13-dioxo-11-(2,2,2-trifluoroacetyl)-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-2-carboxylate
• CAS: 184848-75-7
• 化学式: C₃₃H₄₅F₃O₅
• 分子量: 578.713
• InChiKey: UDXXMUIPFIOKJU-HAVRMCHDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.07
• 重原子数：
  41.0
• 可旋转键数：
  2.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  77.51
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  3,11-dioxo-2-trifluoroacetyl-olean-12-en-30-oic acid methyl ester 在 吡啶 、 羟胺 作用下， 以 乙醇 为溶剂， 生成 11-oxo-3'-trifluoromethyl-olean-12-eno[2,3-d]isoxazol-30-oic acid methyl ester
  参考文献：
  名称：

  Kim,K.-O. et al., Journal of General Chemistry of the USSR, 1970, vol. 40, p. 455 - 459

  摘要：

  DOI：
• 作为产物：
  描述：

  (3beta,20beta)-3-羟基-11-氧代-齐墩果-12-烯-29-酸甲酯 在 sodium hydride 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 12.17h， 生成 3,11-dioxo-2-trifluoroacetyl-olean-12-en-30-oic acid methyl ester
  参考文献：
  名称：

  基于结构的甘草次酸衍生物设计作为针对高迁移率组 Box-1 的强效抗败血症药物

  摘要：

  基于结构设计和合成了在 A 环上具有稠合杂环的新型甘草次酸 (GA) 衍生物。通过经典的 LPS 刺激的巨噬细胞模型研究了它们潜在的抗炎作用。表面等离子体共振 (SPR) 用于验证 GA 类似物与 HMGB1 的结合。总结了初步的构效关系，具有邻甲氧基苄基吡唑的类似物GA-60显示出更强的抗炎作用和更高的 HMGB1 亲和力，K d值为 12.5 μM。此外，该化合物通过干扰 p38、ERK、JNK MAPKs 的磷酸化以及NF-κB p65 和 IKKα/β。而且，GA-60延长了经典 CLP 诱导或 LPS 诱导的败血症小鼠模型的存活时间。分子建模预测进一步支持了这些发现，清楚地表明使用稠合杂环 GA 衍生物抑制 HMGB1 释放是治疗脓毒症的一种有前途的策略。

  DOI：

  10.1016/j.bioorg.2020.104461

文献信息

• Synthesis of Novel Heterocyclic Ring-Fused 18<i>β</i>-Glycyrrhetinic Acid Derivatives with Antitumor and Antimetastatic Activity
  作者：Cheng Gao、Fu-Jun Dai、Hai-Wei Cui、Shi-Hong Peng、Yuan He、Xue Wang、Zheng-Fang Yi、Wen-Wei Qiu

  DOI：10.1111/cbdd.12308

  日期：2014.8

  Glycyrrhetinic acid (GA) is one of the most important triterpenoic acids shows many pharmacological effects, especially antitumor activity. GA triggers apoptosis in various tumor cell lines. However, the antitumor activity of GA is weak, thus the synthesis of new synthetic analogs with enhanced potency is needed. By introducing various five‐member fused heterocyclic rings at C‐2 and C‐3 positions, 18 novel GA derivatives were obtained. These compounds were evaluated for their inhibitory activity against the growth of eight different tumor cell lines using a SRB assay. The most active compound 37 showed IC50 between 5.19 and 11.72 μm, which was about 11‐fold more potent than the lead compound GA. An apoptotic effect of GA and 37 was determined using flow cytometry and trypan blue exclusion assays. We also demonstrated here for the first time that GA and the synthetic derivatives exhibited inhibitory effect on migration of the tested tumor cells, especially 37 which was about 20‐fold more potent than GA on antimetastatic activity.