Synthesis, anti-cancer activity and molecular docking studies of new nicotinamide containing EP4 antagonists

•20 new EP4 antagonists compounds designed and synthesized based on the literature nicotinamide derivative AAT-008.•Evaluations of the in vitro EP4 antagonistic activity, analysis of the SAR and structure optimizations, the most potent compound 14 was obtained which had good solubility and microsomal metabolic stability.•In cytotoxicity assays, compound 14 was weakly active in breast cancer cell line and moderately active in colon cancer cell lines (under PGE2 induced conditions).•The trend in EP4 activity range was explained with aid of molecular docking studies.