Synthesis of novel N-aryl-4-[6-(2-fluoropyridin-3-yl)quinazolin-2-yl]-piperazine-1-carboxamide or -carbothioamide derivatives and their antimicrobial activity

Abstract

Quinazolines are heterocyclic compounds with an important place in the field of medicinal chemistry. The quinazoline ring system is present in the structure of approximately 150 naturally occurring pharmacologically active alkaloids, isolated from a number of families of the plant and animal kingdom, as well as various microorga- nisms. 1 Quinazoline derivatives possess diverse biological and therapeutic activities such as antibacterial, 2-4 antifun- gal, 5 anti-inflammatory, 6 anticancer, 2,7 antituberculosis, 8 A series of novel N-aryl-4-(6-(2-fluoropyridin-3-yl)quinazolin-2-yl)-piperazine-1-carboxamide or -carbothioamide derivatives was synthe- sized by cyclization of 5-bromo-2-fluorobenzaldehyde and guanidine carbonate in the presence of dimethylacetamide followed by treatment with isoamylnitrite and diiodomethane in the presence of copper iodide to afford 6-bromo-2-iodoquinazoline. The latter was treated with piperazine in the presence of triethylamine followed by (2-fluoropyridin-3-yl)boronic acid in the presence of Pd(PPh3)2Cl2 to afford 6-(2-fluoropyridin-3-yl)-2-(piperazin-1-yl)quinazoline which was further treated with various substituted arylisocyanates and arylisothio- cyanates to obtain the title compounds. The chemical structures of the synthesized compounds were confirmed by means of LC-MS, 1 H, 13 C NMR, IR, and mass spectra and elemental analysis. All the synthesized compounds were evaluated for their in vitro antibacterial activity against two Gram-positive and two Gram-negative bacterial species, as well as two different strains of antibiotic-resistant E. coli and for antifungal activity against two fungal strains. Some of the compounds have shown potential antimicrobial activity.