Discovery and structure–activity relationship of 2-phenyl-oxazole-4-carboxamide derivatives as potent apoptosis inducers

As a continuation of our efforts to discover novel apoptosis inducers as anticancer agents using a cell-based caspase HTS assay, 2-phenyl-oxazole-4-carboxamide derivatives were identified. The structure–activity relationships of this class of molecules were explored. Compound 1k, with EC50 of 270 nM and GI50 of 229 nM in human colorectal DLD-1 cells, was selected and demonstrated the ability to cleave PARP and displayed DNA laddering, the hallmarks of apoptosis. Compound 1k showed 63% tumor growth inhibition in human colorectal DLD-1 xenograft mouse model at 50 mpk, bid.

Graphical abstractNovel 2-phenyl-oxazole-4-carboxamide-containing apoptosis inducers were discovered from a cell-based assay for caspase-3 activation. Synthesis, in vitro, and in vivo activity profiles are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide