Synthesis, biological activity studies and computer-assisted calculations of 4-aminoacid substituted quinazoline-2-carboxylates

Nitrogen-containing heterocyclic compounds are widely used in synthetic drugs, bioactive natural products, pharmaceuticals, agrochemicals and have an integral scaffold. Among such compounds, quinazolines constitute an important class of heterocyclic compounds due to their various medicinal properties. In this thesis, starting from 2-amino benzoic acid, the -OH group of 2-amino benzoic acid was functionalized with benzotriazole group and ethyl 4-oxo-3,4-dihydroquinazoline-2-carboxylate compounds were synthesized. Then, ethyl 4-chloroquinazoline-2-carboxylate derivatives were obtained by reaction of these compounds with SOCl2. Finally, ethyl (L)4-((1-methoxy-1-oxopropan-2-yl)amino)quinazolin-2-carboxylate derivatives were obtained by reaction of these compounds with L-Alanine methyl ester (hydrochloride). The structures of the synthesized compounds were elucidated by 1HNMR, 13CNMR, IR, elemental analysis methods. In addition, computer-aided calculations of all compounds were performed by DFT method. Finally, the cytotoxic effects and EGFR enzyme inhibition activities of all compounds on MCF7, A549 and NIH3T3 cell lines were investigated. Structure-based in silico docking method was developed to determine the possible interaction and binding points of the compound showing the strongest inhibition effect on EGFR enzyme. Among compounds 95a-h, 95c and 95d showed the highest biological activity.