LAUSR

To obtain more active and selective anti-platelet candidate drugs, we tried to introduce a methyl group at the 5-position and 6-position of the parent benzene ring first time, respectively or simultaneously. The idea could inspect compound with tetra-substituted or penta-substituted characteristics rather than retained classical 1,3,4-position triple substitutions characteristic whether it continues to have anti-platelet activity in vitro. The biological evaluation revealed that most of compounds with this novel structure were more potent than the positive control drug Picotamide. At the concentration of 1.3 μmol/L, using Arachidonic acid as an inducer, it was found that the anti-platelet activity in vitro of five compounds 1a, 1b, 1c, 2f, and 3d was higher than that of Picotamide and the series 1 compounds were generally higher than that of the series 2 and 3. And with ADP as an inducer, the activity in vitro of nine compounds 2a, 2b, 2d, 2f, 2g, 2h, 3a, 3b, and 3c was more elevated than that of Picotamide and the compounds of series 2 and 3 were all evidently even more active than that of series 1. The proportion of newly designed target compounds with active is higher than that of previously developed series of compounds. Based on the in vitro activity results, a preliminary analysis of the structure–activity relationship was deduced. Meanwhile, cytotoxic effects in vitro of 11 target compounds 1b, 1c, 2f, 2a, 2b, 3a, 3b, 3c, 2d, 2g, and 2h on L-929 cells were analyzed, but the data analysis shows that at two concentrations, target compounds have higher effect on L-929 cells than that of control drug Picotamide. The reason or mechanism for obtaining higher in vitro activity and higher cytotoxicity of the target compound under tetra- or penta- substitutions requires further relevant research work before conclusion can be drawn.