<i>In-Silico</i> Evaluation, Chemical Reactivity, and Covalent Docking Study of Various Quinazolines and Pyridopyrimidines as Inhibitors for the Epidermal Growth Factor Receptor

The epidermal growth factor receptor (EGFR) sensitivity to tyrosine kinase inhibitors gefitinib and erlotinib-activated mutants is common in non-small cell lung cancer. An in-silico screening study of quinazolines pyridopyrimidines against the wild-type (WT) mutation EGFR was conducted, employing several computational approaches such as covalent docking molecular dynamics simulation followed by reactivity absorption, distribution, metabolism, excretion, toxicity (ADMET). Twenty-two heterocyclic compounds were screened WT mutated proteins (L858R T790M). Compounds 4 19, which contain quinazoline[3,4-d]pyrimidine pyrido[3,4-d]pyrimidine, respectively, found have an affinity toward mutant protein. In addition, they had good chemical kinetic stability mutations desirable ADMET properties. These findings reveal new, robust, irreversible for its proteins.