The IMDAV approach towards thieno- and furoisoindolo[2,1-a]quinazolines-11(13)-carboxylic acids possessing antimicrobial and antiviral activities

Interaction of 2-furylvinyl- and 2-thienylvinyl-2,3-dihydroquinazolin-4(1H)-ones with maleic anhydride gives isoindolo[2,1-a]quinazoline-11(13)-carboxylic acids via the tandem acylation/intramolecular Diels-Alder reaction of vinylarenes (IMDAV). The reaction sequence involves three successive steps: the initial acylation of a quinazolinone nitrogen atom, the IMDAV reaction, and the final aromatization of the resulting five-member ring. The proposed exo-cycloaddition reaction allows to construct from four to five stereogenic centers and two new rings in one synthetic step. The target annelated isoindoloquinazolines were evaluated in vitro against common bacterial pathogens strains (Escherichia coli, Staphylococcus aureus, etc.). It was demonstrated that some of thienoisoindolequinazoline derivatives exibit a potent antibacterial activity at the level of MIC values of 16–32 μg mL−1. Selected 2,3-dihydroquinazolin-4(1H)-ones and isoindolo[2,1-a]quinazolinecarboxylic acids displayed antiviral activity (against the influenza virus A/Puerto Rico/8/34 – H1N1). © 2022 Elsevier Ltd