Synthesis of new 2,3-disubstituted quinazoline-4(3H)-one derivatives and investigation of their biological properties

This thesis study comprises the synthesis of novel potential bioactive compounds containing a combination of quinazolinone structures with various heterocycle, which are used as pharmaceutically active agents due to their important biological and pharmacological properties, and investigation of various enzyme inhibition properties of these molecules. At the first, iminoester hydrochlorides (1a-f) were synthesized by the method described in the literature and the starting quinazolinones (2a-f) were obtained by reacting these compounds with 2-aminobenzamide. With the reaction of the compounds 2a-f with ethylbromoacetate the ester derivatives (3a-f) and with the reaction of these pruducts by hydrazine hydrate, the hydrazide derivative quinazolinones (4a-f), were synthesized. The target compounds 6a-f, which containing the oxadiazole ring were obtained by the reaction of 4a-f compounds with CS2 and which containing the furan ring were obtained by the reaction of the compounds 4a-f with acid-catalyzed heating. Also, thiosemicarbazide derivatives were obtained (8a-f) by the reaction of the compounds 4a-f with ethyl isothiocyanate and with intramolecular cyclization of these intermediates in acidic medium, thiadiazole containing quinazolinone derivates (9a-f) were synthesized. At the last step of the work, 4a-f compounds were converted to quinazolinone-coumarin hybrid compounds (7a-f) utilizing benzotriazole chemistry. Thus, 54 quinazolinone derivatives which of 42 were original, were synthesized and the urease, lipase and α-glucosidase enzyme inhibition properties of these compounds were investigated by elucidating the structures of these novel compounds by IR, 1H-NMR, 13C-APT and mass spectra. Most specifically, it was observed that the urease inhibition data were remarkable. The best urease inhibitor is 6b and its IC50 value is 1,55±0,11µg/mL.