Key Laboratory of Drug Targeting and Drug Delivery System of Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, China.
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Bioorg Med Chem Lett. 2023 Apr 15;86:129238. doi: 10.1016/j.bmcl.2023.129238. Epub 2023 Mar 15.
The ongoing COVID-19 pandemic has led to massive infections and deaths and caused tremendous grief among the people. Although vaccines have played an important role in fighting COVID-19, the situation that the protective effect of current vaccines significantly decreases against mutated strains reminds us of the pressing need for developing effective antiviral therapeutics. The main protease (M) is a key enzyme for SARS-CoV-2 viral replication and transcription and an attractive target for drug development. In this research, we report a new series of M inhibitors containing 3-phenyl-1,2,4-oxadiazole. Structure-activity relationship (SAR) studies led to the discovery of the most active compound, 16d, which showed an IC value of 5.27 ± 0.26 μM. Collectively, we obtained a new small molecular inhibitor targeting SARS-CoV-2 M, which contains a new scaffold. This compound could be taken as a lead compound for subsequent drug discovery against SARS-CoV-2.
持续的 COVID-19 大流行导致了大规模的感染和死亡，给人们带来了巨大的悲痛。尽管疫苗在抗击 COVID-19 方面发挥了重要作用，但当前疫苗对突变株的保护效果显著下降的情况提醒我们，迫切需要开发有效的抗病毒治疗药物。主蛋白酶（M）是 SARS-CoV-2 病毒复制和转录的关键酶，也是药物开发的一个有吸引力的靶点。在这项研究中，我们报告了一系列包含 3-苯基-1,2,4-噁二唑的新型 M 抑制剂。构效关系（SAR）研究发现了最活跃的化合物 16d，其 IC 值为 5.27±0.26μM。总的来说，我们获得了一种针对 SARS-CoV-2 M 的新型小分子抑制剂，它包含了一个新的支架。该化合物可以作为针对 SARS-CoV-2 的后续药物发现的先导化合物。
