Department of Chemistry and Physics, Augusta University, Augusta, GA, 30912, USA.
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.
ChemMedChem. 2021 Nov 19;16(22):3418-3427. doi: 10.1002/cmdc.202100476. Epub 2021 Sep 6.
Currently, limited therapeutic options are available for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We have developed a set of pyrazine-based small molecules. A series of pyrazine conjugates was synthesized by microwave-assisted click chemistry and benzotriazole chemistry. All the synthesized conjugates were screened against the SAR-CoV-2 virus and their cytotoxicity was determined. Computational studies were carried out to validate the biological data. Some of the pyrazine-triazole conjugates (5 d-g) and (S)-N-(1-(benzo[d]thiazol-2-yl)-2-phenylethyl)pyrazine-2-carboxamide 12 i show significant potency against SARS-CoV-2 among the synthesized conjugates. The selectivity index (SI) of potent conjugates indicates significant efficacy compared to the reference drug (Favipiravir).
目前，针对严重急性呼吸综合征冠状病毒 2 型（SARS-CoV-2）的治疗方法有限。我们开发了一组基于哒嗪的小分子。通过微波辅助点击化学和苯并三唑化学合成了一系列哒嗪缀合物。所有合成的缀合物都针对 SARS-CoV-2 病毒进行了筛选，并测定了它们的细胞毒性。进行了计算研究以验证生物学数据。在合成的缀合物中，一些哒嗪-三唑缀合物（5d-g）和（S）-N-（1-（苯并[d]噻唑-2-基）-2-苯乙基）哒嗪-2-甲酰胺 12i 对 SARS-CoV-2 表现出显著的活性。与参考药物（法匹拉韦）相比，有效缀合物的选择性指数（SI）表明其具有显著的疗效。
