The COVID-19 pandemic is ongoing as of mid-2022 and requires the development of new therapeutic drugs, because the existing clinically approved drugs are limited. In this work, seven derivatives of epoxybenzooxocinopyridine were synthesized and tested for the ability to inhibit the replication of the SARS-CoV-2 virus in cell cultures. Among the described compounds, six were not able to suppress the SARS-CoV-2 virus’ replication. One compound, which is a derivative of epoxybenzooxocinopyridine with an attached side group of 3,4-dihydroquinoxalin-2-one, demonstrated antiviral activity comparable to that of one pharmaceutical drug. The described compound is a prospective lead substance, because the half-maximal effective concentration is 2.23 μg/μL, which is within a pharmacologically achievable range.

The multicomponent reaction of 2-nitroacetophenone (or nitroacetone), acetaldehyde diethyl acetal, β-dicarbonyl compound, and ammonium acetate in an acetic acid solution allowed the acquisition of previously undescribed 4-methyl-substituted derivatives of 5-nitro-1,4-dihydropyridine in satisfactory yields. The oxidation of the obtained 5-nitro-1,4-dihydropyridine derivatives resulted in the corresponding 2,4-dimethyl-5-nitropyridines. In addition, for the first time in the synthesis of unsymmetrical 1,4-dihydropyridines by the Hantzsch reaction acetaldehyde, diethyl acetal was used as a source of acetaldehyde. The use of more volatile and sufficiently reactive acetaldehyde in this reaction did not lead to a controlled synthesis of unsymmetrical 5-nitro-1,4-dihydropyridines. The proposed multicomponent approach to the synthesis of 4-methyl-substituted 5-nitro-1,4-dihydropyridines and their subsequent aromatization into pyridines made it possible to obtain previously undescribed and hardly accessible substituted 5(3)-nitropyridines.

Multicomponent reaction of 2-nitroacetophenone, urotropine (or paraformaldehyde), β-dicarbonyl compound and ammonium acetate afforded five new 4-unsubstituted 5-nitro-6-phenyl-1,4-dihydropyridine derivatives, oxidation of which provided the corresponding 5-nitro-6-phenylpyridines. The proposed approach for the synthesis of 4-unsubstituted 5-nitro-6-phenyl-1,4-dihydropyridines and their subsequent aromatization into pyridines made it possible to reduce the total reaction time by more than 200 times and the overall yield of 5-nitro-6-phenylpyridine by 2 times compared with the known methods.

Claisen condensation reaction of diethyl oxalate with 1-[4-(furan-2-yl)-2-methyl-5-nitro-6-phenylpyridin-3-yl]ethan-1-one afforded (Z)-4-[4-(furan-2-yl)-2-methyl-5-nitro-6-phenylpyridin-3-yl]-2-hydroxy-4-oxobut-2-enoic acid. The latter reacted with various binucleo­philes to form the corresponding 3,4-dihydroquinoxaline-2(1H)-one, 3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one, and 1H-pyrazole derivatives. Biological screening of the obtained compounds revealed analgesic and antibacterial activity.