Design, synthesis, and biological evaluation of novel 6-aminoalkyl- and 7-heteroaryl substituted 7-deazapurine nucleoside analogs against SARS-CoV-2 replication.
Guoqiang Yao, Xue Shi, Hao Jiang, Anna Duan, Jiancun Zhang
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引用次数: 0
Abstract
Despite the declaration by the WHO on May 5th of 2023 that the COVID-19 epidemic no longer constitutes a Public Health Emergency of International Concern (PHEIC), it continues to pose a significant threat to human health due to ongoing viral mutations. Although multiple vaccines and drugs have received approval for the prevention and treatment of COVID-19, effectively controlling the epidemic continues to be challenging, emphasizing the necessity for the development of new and more effective antivirals. In this work, we report the design and synthesis of a series of novel 7-alkynyl-7-deazapurine nucleoside analogs and some of their corresponding prodrugs as potential inhibitors of SARS-CoV-2 replication. The biological activities were evaluated and a reasonable structure-activity relationship (SAR) was revealed. Among the compounds, compound 54 (EC50 = 0.71 μM) and 30c (EC50 = 0.66 μM) may serve as potential candidates for further development.
期刊介绍：
Antiviral Research is a journal that focuses on various aspects of controlling viral infections in both humans and animals. It is a platform for publishing research reports, short communications, review articles, and commentaries. The journal covers a wide range of topics including antiviral drugs, antibodies, and host-response modifiers. These topics encompass their synthesis, in vitro and in vivo testing, as well as mechanisms of action. Additionally, the journal also publishes studies on the development of new or improved vaccines against viral infections in humans. It delves into assessing the safety of drugs and vaccines, tracking the evolution of drug or vaccine-resistant viruses, and developing effective countermeasures. Another area of interest includes the identification and validation of new drug targets. The journal further explores laboratory animal models of viral diseases, investigates the pathogenesis of viral diseases, and examines the mechanisms by which viruses avoid host immune responses.
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