Ultrasound assisted synthesis of 3-alkynyl substituted 2-chloroquinoxaline derivatives: their in silico assessment as potential ligands for N-protein of SARS-CoV-2

Shahinshavali, Shaik; Hossain, Kazi Amirul; Kumar, Abbaraju Venkata Durga Nagendra; Reddy, Alugubelli Gopi; Kolli, Deepti; Nakhi, Ali; Rao, Mandava Venkata Basaveswara; Pal, Manojit

In view of recent global pandemic the 3-alkynyl substituted 2-chloroquinoxaline framework has been explored as a potential template for the design of molecules targeting COVID-19. Initial in silico studies of representative compounds to assess their binding affinities via docking into the N-terminal RNA-binding domain (NTD) of N-protein of SARS-CoV-2 prompted further study of these molecules. Thus building of a small library of molecules based on the said template became essential for this purpose. Accordingly, a convenient and environmentally safer method has been developed for the rapid synthesis of 3-alkynyl substituted 2-chloroquinoxaline derivatives under Cu-catalysis assisted by ultrasound. This simple and straightforward method involved the coupling of 2,3-dichloroquinoxaline with commercially available terminal alkynes in the presence of CuI, PPh3 and K2CO3 in PEG-400. Further in silico studies revealed some remarkable observations and established a virtual SAR (Structure Activity Relationship) within the series. Three compound appeared as potential agents for further studies.