assessment and sonochemical synthesis of 2-alkynyl 3-chloropyrazines as prospective ligands for SARS-CoV-2.

The recent global pandemic caused by COVID-19 has triggered an intense effort worldwide towards the development of an effective cure for this disease. In our effort we have explored the 2-alkynyl substituted 3-chloropyrazine framework as a potential template for the design of molecules for this purpose. Our strategy was supported by the studies of representative compounds to assess their binding affinities docking into the N-terminal RNA-binding domain (NTD) of N-protein of SARS-CoV-2. Thus we created a small library of molecules based on the aforementioned template an environmentally safer method that involved the rapid synthesis of 2-alkynyl 3-chloropyrazine derivatives under Cu-catalysis assisted by ultrasound. The reactions proceeded the coupling of 2,3-dichloropyrazine with commercially available terminal alkynes in the presence of CuI, PPh and KCO in PEG-400. Further molecular modelling studies helped in establishing a virtual SAR (Structure Activity Relationship) within the series and identification of three potential hits. The desirable ADME was also predicted for these three molecules suggesting their prospective medicinal value.