Synthesis and In silico Docking Study of Some New Quinazolin-2,4-diones Targeting COVID-19 (SARS-Cov-2) Main Protease: A Search for Anti-Covid19 Drug Candidates

In the present study, a new series of quinazolin-2,4-dione analogues was synthesized by reaction of 4-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3- yl)-benzoyl chloride 1 with several diamines in presence of triethyl amine (TEA) and dioxane. The newly compounds 2-6 were structurally confirmed by means of spectral techniques such as IR, H-1-NMR, C-13-NMR, MS and elemental analysis. Moreover, an in silico molecular docking analysis of the newly compounds was performed to identify new potential therapeutic agents against Covid-19, targeting main protease (Mpro) enzyme. Compound 4 exhibited the highest binding affinity against the selected target. In addition, in silico drug-likeness and ADMET (absorption, distribution, metabolism, excretion, and toxicity) findings exhibited that compound 4 obeyed Lipinski's rule of five (Ro5) and could be used as drug candidate to combat Covid-19 disease.