Synthesis and Molecular Docking Study of Novel Pyrimidine Derivatives against COVID-19

Abstract

A novel series of pyrido[2,3-<i>d</i>]pyrimidines; pyrido[3,2-<i>e</i>][1,3,4]triazolo; and tetrazolo[1,5-<i>c</i>]pyrimidines were synthesized via different chemical transformations starting from pyrazolo[3,4-<i>b</i>]pyridin-6-yl)-<i>N</i>,<i>N</i>-dimethylcarbamimidic chloride <b>3b</b> (prepared from the reaction of <i>o</i>-aminonitrile <b>1b</b> and phosogen iminiumchloride). The structures of the newly synthesized compounds were elucidated based on spectroscopic data and elemental analyses. Designated compounds are subjected for molecular docking by using Auto Dock Vina software in order to evaluate the antiviral potency for the synthesized compounds against SARS-CoV-2 (2019-nCoV) main protease M ^pro. The antiviral activity against SARS-CoV-2 showed that tested compounds <b>7c</b>, <b>7d</b>, and <b>7e</b> had the most promising antiviral activity with lower IC₅₀ values compared to Lopinavir, "the commonly used protease inhibitor". Both in silico and in vitro results are in agreement.