Department of Pharmacy, Federal University of Juiz de Fora,
Governador Valadares, Minas Gerais, Brazil
The development of new drugs can present several problems, such as a molecule that is a potent pharmacological inhibitor and has a possibility in the execution of its synthesis. Quinazolines are known to be capable of inhibitory kinases. Thus, a detailed study was carried out to propose new quinazolines with synthetic routes already known, and that were promising for the ability to inhibit kinases. Lipinski's five-rule in computational studies has been applied to select more promising molecules. In this study, the molecules proposed for the synthesis were systematically designed in appropriate computational programs to test several substituents of the quinazoline nucleus on the capacity of these molecules to be considered inhibitors of kinases. Six molecules were selected with the best results to inhibit kinases. In the study to evaluate the variation of substituents, the result obtained for the 8-position of the quinazoline ring and with the -Cl substituent at that ring position presented 60% of the 10 best molecules capable of inhibiting kinases. The molecular docking study confirmed that the two most promising molecules to inhibit kinase also obtained the best results to inhibit AKT kinase. Therefore, through this study it was possible to select six more promising molecules to be synthesized and available in large screening tests for several therapeutic targets known as High-Throughput Screening.