Structural optimization and biological evaluation of l,5-disubstituted pyrazole-3-carboxamines as potent inhibitors of human 5-lipoxygenase
文献类型：期刊论文
| 作者 | Zhou Yu3 ; Liu Jun2; Zheng Mingyue3; Zheng Shuli1; Jiang Chunyi3; Zhou Xiaomei1; Zhang Dong3; Zhao Jihui3; Ye Deju3; Zheng Mingfang3
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| 刊名 | Acta Pharmaceutica Sinica B
 |
| 出版日期 | 2016 |
| 卷号 | 6期号:1页码:32 |
| 关键词 | 5-Lipoxygenase 5-LOX inhibitors Pyrazole derivatives Leukotrienes-related diseases In vivo Benzo-fused heterocycle Ischemic incults Brain inflammation |
| ISSN号 | 2211-3835 |
| 英文摘要 | Human 5-lipoxygenase (5-LOX) is a well-validated drug target and its inhibitors are potential drugs for treating leukotriene-related disorders. Our previous work on structural optimization of the hit compound 2 from our in-house collection identified two lead compounds, 3a and 3b, exhibiting a potent inhibitory profile against 5-LOX with IC_(50) values less than 1 μmol/L in cell-based assays. Here,we further optimized these compounds to prepare a class of novel pyrazole derivatives by opening the fused-ring system. Several new compounds exhibited more potent inhibitory activity than the lead compounds against 5-LOX. In particular, compound 4e not only suppressed lipopolysaccharide-induced inflammation in brain inflammatory cells and protected neurons from oxidative toxicity, but also significantly decreased infarct damage in a mouse model of cerebral ischemia. Molecular docking analysis further confirmed the consistency of our theoretical results and experimental data. In conclusion, the excellent in vitro and in vivo inhibitory activities of these compounds against 5-LOX suggested that these novel chemical structures have a promising therapeutic potential to treat leukotriene-related disorders. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/294487]  |
| 专题 | 中国科学院上海药物研究所 |
| 作者单位 | 1.中国科学院上海生命科学研究院神经科学研究所 2.中国药科大学 3.中国科学院上海药物研究所 |
| 推荐引用方式 GB/T 7714 | Zhou Yu,Liu Jun,Zheng Mingyue,et al. Structural optimization and biological evaluation of l,5-disubstituted pyrazole-3-carboxamines as potent inhibitors of human 5-lipoxygenase[J]. Acta Pharmaceutica Sinica B,2016,6(1):32. |
| APA | Zhou Yu.,Liu Jun.,Zheng Mingyue.,Zheng Shuli.,Jiang Chunyi.,...&Liu Hong.(2016).Structural optimization and biological evaluation of l,5-disubstituted pyrazole-3-carboxamines as potent inhibitors of human 5-lipoxygenase.Acta Pharmaceutica Sinica B,6(1),32. |
| MLA | Zhou Yu,et al."Structural optimization and biological evaluation of l,5-disubstituted pyrazole-3-carboxamines as potent inhibitors of human 5-lipoxygenase".Acta Pharmaceutica Sinica B 6.1(2016):32. |
入库方式： OAI收割
来源：上海药物研究所
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