A virus outbreak challenges the economic, medical, and public health infrastructure worldwide. More than one virus capable of triggering diseases have been identified per year since 1972, which requires the development of new ways of treatment and prevention, however, such processes are not rapid and easy. With the pandemic scenario experienced since early 2020, several drugs with well-known purposes have gained prominence, due to speculation of their use in the treatment against the new coronavirus. Among the main drugs studied, the vast majority contain a heterocyclic structure. In this review, we presented the traditional and efficient synthesis of 15 drugs that have been studied for the COVID-19 treatment, containing in their structure heterocycles like indole, quinoline, pyrimidone, tetrahydrofuran, pyrrolidine, triazole, pyridazine, pyrazole, pyrrolopyrimidine, azetidine, pyrrolotriazine, pyrazine, tetrahydropyran, benzofuran, spiroketal, and thiazole. Furthermore, we have shown the original applications, as well as their structure–activity relationship and what is their situation as a drug candidate against COVID-19. Thus, the objective was to consolidate the main synthetic and pharmacological aspects involving clinically developed heterocycles that at some point were presented as promising against SARS-CoV-2.

中文翻译：

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杂环化合物作为抗病毒药物：合成、构效关系和传统应用

病毒爆发对全球经济、医疗和公共卫生基础设施构成挑战。自 1972 年以来，每年都会发现不止一种能够引发疾病的病毒，这需要开发新的治疗和预防方法，但是，这样的过程并不快速和容易。随着 2020 年初以来的大流行情况，由于人们猜测它们用于治疗新的冠状病毒，几种具有众所周知用途的药物变得突出。在研究的主要药物中，绝大多数含有杂环结构。在这篇综述中，我们介绍了已研究用于 COVID-19 治疗的 15 种药物的传统有效合成，其结构中含有杂环化合物，如吲哚、喹啉、嘧啶酮、四氢呋喃、吡咯烷、三唑、哒嗪、吡唑、吡咯并嘧啶、氮杂环丁烷、吡咯并三嗪、吡嗪、四氢吡喃、苯并呋喃、螺缩酮和噻唑。此外，我们展示了原始应用，以及它们的构效关系以及它们作为 COVID-19 候选药物的情况。因此，目标是巩固涉及临床开发的杂环化合物的主要合成和药理学方面，这些杂环在某些时候被认为有希望对抗 SARS-CoV-2。