(R)-8-acetyl-5,7-dihydroxy-3,4a,6-trimethyl-1-(p-tolyl)-1,4a-dihydro-4H-benzofuro[3,2-f]indazol-4-one | 1225460-17-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (R)-8-acetyl-5,7-dihydroxy-3,4a,6-trimethyl-1-(p-tolyl)-1,4a-dihydro-4H-benzofuro[3,2-f]indazol-4-one
• 英文别名: 8-acetyl-5,7-dihydroxy-3,4a,6-trimethyl-1-(p-tolyl)-1,4a-dihydro-4H-benzofuro[3,2-f]indazol-4-one
• CAS: 1225460-17-2
• 化学式: C₂₅H₂₂N₂O₅
• 分子量: 430.46
• InChiKey: VNWLBCGGEGRUQX-VWLOTQADSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  32.0
• 可旋转键数：
  2.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  101.65
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  4-甲基苯肼盐酸盐 、 (+)-usnic acid 在 三乙胺 作用下， 以 乙醇 为溶剂， 以46%的产率得到(R)-8-acetyl-5,7-dihydroxy-3,4a,6-trimethyl-1-(p-tolyl)-1,4a-dihydro-4H-benzofuro[3,2-f]indazol-4-one
  参考文献：
  名称：

  Synthesis and Biological Evaluation of (+)-Usnic Acid Derivatives as Potential Anti-Toxoplasma gondii Agents

  摘要：

  Six series of (+)-usnic acid derivatives were synthesized. The IC50 values of these compounds were determined in T. gondii infected HeLa cells (mu M) and in HeLa cells (mu M), and their selectivity indexes (SI) were calculated. In vitro, most of the derivatives tested in this study exhibited more anti activity than that of the parent compound (+)-usnic acid and the positive control drugs. Among these derivatives, methyl (E)-(1-(6-acetyl-7,9-dihydroxy-8,9b-dimethyl-1,3-dioxo-3,9b-dihydrodibenzo[b,d]furan-2(1H)-ylidene)ethyl)phenylalaninate (D3) showed the most effective anti-T. gondii activity (selectivity >2.77). In comparison with the clinically used positive control drugs sulfadiazine (selectivity 1.15), pyrimethamine (selectivity 0.89), spiramycin (selectivity 0.72), and the lead compound (+)-usnic acid (selectivity 0.96), D3 showed better results in vitro. Furthermore, D3 and (E)-6-acetyl-7,9-dihydroxy-8,9b-dimethyl-2-(1-(quinolin-6-ylamino)ethylidene)dibenzo[b,d]furan-1,3-(2H,9bH)-dione (F3) had greater inhibitory effects on T. gondii (inhibition rates 76.0% and 64.6%) in vivo in comparison to spiramycin (inhibition rate 55.2%); in the peritoneal cavity of mice, the number of tachyzoites was significantly reduced (p < 0.001) in vivo. Additionally, some biochemical parameters were measured and spleen indexes were comprehensively evaluated, and the results indicated that mice treated with both compound D3 and compound F3 showed reduced hepatotoxicity and significantly enhanced antioxidative effects in comparison to the normal group. Granuloma and cyst formation were effected by the inhibition of compound D3 and compound F3 in liver sections. Overall, these results indicated that D3 and F3 for use as anti-T. gondii agents are promising lead compounds.

  DOI：

  10.1021/acs.jafc.9b02173