Synthesis, antiproliferative and 4D-QSAR studies of thiadiazole derivatives bearing acrylamide moiety as EGFR inhibitors.

ABSTRACT

As a target for clinical anti-cancer treatment, epidermal growth factor receptor (EGFR) exhibits its over-expression on various tumour cells and is associated with the development of a variety of human cancers. Herein, we described the synthesis, antiproliferative activity assay and 4D-QSAR studies of thiadiazole derivatives bearing acrylamide moiety as EGFR inhibitors. Compared with Gefitinib, some of the target compounds have excellent antiproliferative activities against EGFR-expressed A431 cell line. The robust and reliable 4D-QSAR was constructed using comparative distribution detection algorithm, ordered predictors selection and genetic algorithm method, and the following acceptable statistics are shown r2 = 0.82, Q2LOO = 0.67, Q2LMO = 0.61, r2Pred = 0.78.