Design, synthesis and biological activities of novel oxazolo[4,5-g]quinazolin-2(1H)-one derivatives as EGFR inhibitors

A series of oxazolo[4,5-g]quinazolin-2(1H)-one derivatives employing Erlotinib as lead compound were synthesized and evaluated for their EGFR inhibition activity. These compounds having variation at the 1 and 8-position, included ether and esters hydrophilic side-chain and aromatic head fragment, respectively. All these compounds were evaluated by EGFR inhibition and two anti-proliferation assays in vitro. Four compounds were found more potent than Erlotinib in EGFR-TK assay. Furthermore, compounds 18, 42 and 50 also had good to excellent anti-proliferation activity against human epidermoid cancer cell line (KB) and renal cell carcinoma cell line (A498). Finally, compound 50 presented remarkably higher inhibition efficacy towards tumor growth than Erlotinib in a mouse lewis lung cancer (LLC) xenograft model. Furthermore, compound 50 displayed the most distinguished effect on extending the survival period of the tumor-bearing mice. [Display omitted] •Novel oxazolo[4, 5-g]quinazolin-2(1H)-one derivatives were synthesized.•Four compounds found more potent than Erlotinib in EGFR-TK assay.•Comp. 50 had better activity against KB and A498 cell lines than Erlotinib.•Comp. 50 presented higher in vivo antitumor activity than Erlotinib.