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.
Eur J Med Chem. 2022 Jan 15;228:114033. doi: 10.1016/j.ejmech.2021.114033. Epub 2021 Dec 1.
A series of novel biaryl amide derivatives were synthesized and evaluated for anti-HCV virus activity. Some significant SARs were uncovered. The intensive structural modifications led to fifteen novel compounds with more potent inhibitory activity compared to the hit compounds IMB 26 and IMB1f. Among them, compound 80 was the most active, with EC values almost equivalent to the clinical drug telaprevir (EC = 15 nM). Furthermore, it also had a good safety and in vitro and oral pharmacokinetic (oral bioavailability in rats: 34%) profile, suggesting a highly drug-like nature. Compound 80represents a more promising scaffold for anti-HCV virus activity for further study.
我们合成了一系列新型联苯酰胺衍生物，并对其抗 HCV 病毒活性进行了评估。发现了一些显著的 SAR。通过深入的结构修饰，得到了 15 种新型化合物，与先导化合物 IMB 26 和 IMB1f 相比，它们具有更强的抑制活性。其中，化合物 80 最为活跃，EC 值几乎与临床药物特拉匹韦（EC = 15 nM）相当。此外，它还具有良好的安全性和体内、口服药代动力学（大鼠口服生物利用度：34%）特征，表明其具有较高的类药性。化合物 80 代表了一种更有前途的抗 HCV 病毒活性骨架，值得进一步研究。
