Synthesis of New bis-furanyl-pyrrolo[3,4-b]pyridin-5-ones via the Ugi-Zhu Reaction and Docking Studies on the Main Protease (MPro) from SARS-CoV-2

Abstract

: The synthesis of five new bis -furanyl-pyrrolo[3,4-b ]pyridin-5-ones in 30 to 40% yields through a domino sequence based on the Ugi-Zhu three-component reaction is described. Then, on the main protease M Pro (PDB: 6lu7) from the SARS-CoV-2, the synthesized products and co-crystallized ligands of M Pro were in silico evaluated using the docking technique, finding moderate to good binding energies and some interesting interactions, demonstrating that the ligand 8c can be considered as a drug candidate against the SARS-CoV-2-M Pro due to its LE value ( − 5.96 kcal/mol), which is better than other synthesized and reported molecules in the literature. At the same time, hydrophobic interactions play a crucial role in the ligand target molecular couplings, demonstrated through a hydrophobicity surfaces analysis. Finally, 8a and 8b can also be considered as drug candidates. Thus, some synthesized bis -furanyl-pyrrolo[3,4-b ]pyridin-5-ones may be used for further in vitro assays against the virus.