Direct evidence of edge-to-face CH/π interaction for PAR-1 thrombin receptor activation

•Three structural isomers of l-tetrafluorophenylalanine (F4)Phe were synthesized.•Each isomer has only one H atom at the ortho, meta, or para position of Phe-phenyl.•Isomers were incorporated into the PAR-1 receptor–tethered ligand S/Phe/LLRNP.•Two of isomers exhibited noticeable activity in the platelet aggregation assay.•Phe-phenyl benzene-H atoms were found necessary to activate PAR-1 receptor.