Synthesis of New <i>bis</i>-furanyl-pyrrolo[3,4-<i>b</i>]pyridin-5-ones via the Ugi-Zhu Reaction and Docking Studies on the Main Protease (M^Pro) 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 MPro (PDB: 6lu7) from the SARS-CoV-2, the synthesized products and co-crystallized ligands of MPro 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-MPro 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.

Keywords

• Ugi-Zhu reaction
• polyheterocycles
• docking
• COVID-19
• SARS-CoV-2
• main protease M^Pro