(R)-8-acetyl-1-(3-chlorophenyl)-5,7-dihydroxy-3,4a,6-trimethyl-1,4a-dihydro-4H-benzofuro[3,2-f]indazol-4-one | 1225460-13-8

• 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-1-(3-chlorophenyl)-5,7-dihydroxy-3,4a,6-trimethyl-1,4a-dihydro-4H-benzofuro[3,2-f]indazol-4-one
• 英文别名: (R)-8-acetyl-1-(3-chlorophenyl)-5,7-dihydroxy-3,4a,6-trimethyl-1H-benzofuro[3,2-f]indazol-4(4aH)-one；8-acetyl-1-(3-chlorophenyl)-5,7-dihydroxy-3,4a,6-trimethyl-1,4a-dihydro-4H-benzofuro[3,2-f]indazol-4-one
• CAS: 1225460-13-8
• 化学式: C₂₄H₁₉ClN₂O₅
• 分子量: 450.878
• InChiKey: AVWJCAIXFIIYGC-DEOSSOPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.64
• 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：
  0.21
• 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：

  3-氯苯肼盐酸盐 、 (+)-usnic acid 在 吡啶 作用下， 以 乙醇 为溶剂， 反应 12.0h， 以81%的产率得到(R)-8-acetyl-1-(3-chlorophenyl)-5,7-dihydroxy-3,4a,6-trimethyl-1,4a-dihydro-4H-benzofuro[3,2-f]indazol-4-one
  参考文献：
  名称：

  新型（+）-松萝酸类似物的合成及其抗增殖活性。

  摘要：

  合成了二十一种新的（+）-松香酸类类似物，属于三类，例如烯胺，亚胺和吡唑。所有合成的化合物均通过其光谱数据（1 H NMR，13 C NMR，IR和HRMS）进行表征。通过使用SRB细胞增殖测定法评估了合成的化合物对一组包括HeLa（子宫颈），MDA-MB-231（乳腺），A549（肺）和MiaPaca（胰腺）的四种人类癌细胞系的抗增殖活性。筛选结果表明，所有合成的化合物均显示出比母体化合物更高的活性。最重要的是，化合物2e和4a对所有测试的癌细胞系均显示出强大的抗增殖活性。化合物2e和4a使细胞周期停滞在G2 / M期并诱导HeLa细胞凋亡。

  DOI：

  10.1080/10286020.2019.1603220

文献信息

• Synthesis and Biological Evaluation of (+)-Usnic Acid Derivatives as Potential Anti-<i>Toxoplasma gondii</i> Agents
  作者：Hong-Yan Guo、ChunMei Jin、Hai-Ming Zhang、Chun-Mei Jin、Qing-Kun Shen、Zhe-Shan Quan

  DOI：10.1021/acs.jafc.9b02173

  日期：2019.8.28

  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.