Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, PR China.
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, PR China.
Eur J Med Chem. 2020 Nov 15;206:112706. doi: 10.1016/j.ejmech.2020.112706. Epub 2020 Aug 7.
It is an urgent need to develop more effective anti-influenza agents due to the emergence of highly pathogenic and drug-resistant influenza viruses. Herein, a series of 2,4-disubstituted quinazoline derivatives were designed, synthesized and their antiviral activities against influenza A virus were evaluated. Nine compounds (10a2, 16a, 16e, 16i, 16j, 16n, 16o, 16p and 16r) showed potent activity against influenza A virus (IAV) with IC at the low-micromole level (1.29-9.04 μM). Particularly, 16e and 16r possess good anti-IAV activity (IC: 1.29 μM and 3.43 μM, respectively) and acceptable cytotoxicity, and inhibit the transcription and replication of viral RNA. Together with reasonable PK profiles of 16e, these results suggest their promising potential as candidates for further investigation.
由于高致病性和耐药性流感病毒的出现，开发更有效的抗流感药物已成为当务之急。在此，设计、合成了一系列 2,4-取代喹唑啉衍生物，并评估了它们对甲型流感病毒（IAV）的抗病毒活性。其中 9 种化合物（10a2、16a、16e、16i、16j、16n、16o、16p 和 16r）对 IAV 表现出较强的活性，IC 值处于低微摩尔水平（1.29-9.04 μM）。特别是化合物 16e 和 16r 具有良好的抗 IAV 活性（IC 分别为 1.29 μM 和 3.43 μM）和可接受的细胞毒性，能够抑制病毒 RNA 的转录和复制。化合物 16e 还具有合理的 PK 特征，这些结果表明它们具有作为进一步研究候选药物的潜力。
