Non-small cell Lung cancer (NSCLC) is the most common type of lung cancer, which is
caused by high consumption of tobacco and smoking. It is an epithelial lung cancer that affects
about 2.2 million people across the globe, according to International Agency for Research on Cancer
(IARC). Non-small cell lung cancer is a malignant tumor caused by EGFR mutation that occurs
in the in-frame deletion of exon 19 and L858R point mutation in exon 21. Presently, clinically
available inhibitors of EGFR (including erlotinib, lapatinib, gefitinib, selumetinib, etc.) are not specific
and responsible for undesirable adverse effects. Moreover, to solve this problem search for
newer EGFR inhibitors is the utmost need for the treatment and/or management of increasing lung
cancer burden. The discovery of therapeutic agents that inhibit the specific target in tumorous cells,
such as EGFR, is one of the successful strategies in treating many cancer therapies, including lung
cancer. The exhaustive literature survey (2018-2023) has shown the importance of medicinally privileged
pyrimidine derivatives together, fused and/or clubbed with other heterocyclic rings to design
and develop novel EGFR inhibitors. Pyrimidine derivatives substituted with phenylamine, indole,
pyrrole, piperazine, pyrazole, thiophene, pyridine and quinazoline derivatives substituted with phenylamine,
pyrimidine, morpholine, pyrrole, dioxane, acrylamide, indole, pyridine, furan, pyrimidine,
pyrazole etc. are privileged heterocyclic rings shown promising activity by inhibiting EGFR and
TKIs. The present review summarizes the structure-activity relationship (SAR) and enzyme inhibitory
activity, including IC50 values, percentage inhibition, and kinetic studies of potential compounds
from various literature. The review also includes various aspects of molecular docking studies
with compounds under clinical trials and patents filed on pyrimidine-based EGFR inhibitors in
treating non-small cell lung cancer. The present review may benefit the medicinal chemist for developing
novel compounds such as EGFR inhibitors.
