In this manuscript, we are motivated to investigate the reaction site-selectivity for the hydrazo thiazole derivatives (a–c) with different types of active methylene groups such as malononitrile, and ethyl cyanoacetate. Based on their structural investigations and spectrum data, the results of these reactions have been established to be iminopyridazines (a–c) and 6-oxopyridazine derivatives (a–c). We tested the ability of the newly synthesized pyridazine derivatives to inhibit the microbes and COVID-19 proteins. Human coronavirus 229E (HCoV-229E) was used to investigate the antiviral efficacy of prepared compounds. Green monkey kidney (Vero-E6) cell lines were used to investigate MTT and cytopathic effect (CPE). The new 6-oxopyridazine derivatives (a–c) revealed significant inhibitory efficacy and were capable of inhibiting the human coronavirus 229E. Moreover, the antimicrobial result showed that compounds iminopyridazine (c) followed by iminopyridazine (a) followed by iminopyridazine (b) exhibited excellent antimicrobial properties toward all utilized strains, usually greater than that of common reference drugs, with MIC values ranging from 13 to 21 ppm, from 9 to 14 ppm, and from 8 to 19 ppm whereas, the remaining substances appeared to be promising effective. Structure-activity relationship (SAR) revealed that pyridazine scaffolds containing NH group, as well as substituted electron withdrawal group (Cl) in -position for benzene ring attributed to thiazole moiety have the best activity. The current study successfully illustrated the possible application of heterocyclic derivatives with pyridazie nucleus including thiazole ring as the main compound in the development of dual antiviral (COVID-19) and antibacterial pharmaceuticals in the future.

中文翻译：

---

作为抗菌和抗病毒候选药物的新型噻唑-哒嗪衍生物：合成与应用

在这篇手稿中，我们的动机是研究具有不同类型活性亚甲基（例如丙二腈和氰基乙酸乙酯）的亚肼基噻唑衍生物（a-c）的反应位点选择性。根据结构研究和光谱数据，这些反应的结果已确定为亚氨基哒嗪 (a–c) 和 6-氧代哒嗪衍生物 (a–c)。我们测试了新合成的哒嗪衍生物抑制微生物和 COVID-19 蛋白的能力。使用人类冠状病毒 229E (HCoV-229E) 研究制备的化合物的抗病毒功效。使用绿猴肾 (Vero-E6) 细胞系研究 MTT 和细胞病变效应 (CPE)。新型6-氧代哒嗪衍生物(a–c)显示出显着的抑制功效，能够抑制人类冠状病毒229E。此外，抗菌结果表明，化合物亚氨基哒嗪（c）、亚氨基哒嗪（a）、亚氨基哒嗪（b）对所有使用的菌株均表现出优异的抗菌性能，通常大于常见的参考药物，MIC值范围为13至21 ppm、9 至 14 ppm 和 8 至 19 ppm，而其余物质似乎有希望有效。构效关系（SAR）表明，含有NH基团以及噻唑部分苯环-位取代吸电子基团（Cl）的哒嗪支架具有最佳活性。目前的研究成功阐明了以噻唑环为主要化合物的哒嗪核杂环衍生物在未来开发双重抗病毒（COVID-19）和抗菌药物中的可能应用。