Hebei Key Laboratory of Organic Functional Molecules, College of Chemistry and Materials Science, Hebei Normal University, Shijiazhuang 050024, PR China; Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, PR China.
Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, PR China.
Bioorg Med Chem Lett. 2022 May 15;64:128681. doi: 10.1016/j.bmcl.2022.128681. Epub 2022 Mar 15.
We designed and synthesized 18 substituted indole derivatives containing a triazole scaffold as novel anti-influenza A virus candidates using a bio-isosteric and scaffold-hopping strategy from the lead compound 4-32-2. Most of the target compounds (eg: 6, 7a, 7d, 7f-j, 7l, 7m, 7o, 7q) exhibited potent anti-influenza A virus activity and low cytotoxicity in vitro. In particular, 7a exhibited the most potent anti-IAV activity (IC: 1.34 ± 0.13 μM) with low cytotoxicity (CC: > 100 μM), and high selectivity index (SI: > 74.63), which provides a new chemical scaffold for the development of novel anti-IAV drug.
我们设计并合成了 18 种含有三唑支架的取代吲哚衍生物，作为新型抗流感 A 病毒候选物，使用了先导化合物 4-32-2 的生物等排和支架跳跃策略。大多数目标化合物（例如：6、7a、7d、7f-j、7l、7m、7o、7q）在体外表现出很强的抗流感 A 病毒活性和低细胞毒性。特别是 7a 表现出最强的抗 IAV 活性（IC：1.34±0.13 μM），细胞毒性低（CC：>100 μM），选择性指数高（SI：>74.63），为开发新型抗 IAV 药物提供了新的化学结构。
