Synthesis, In Vitro Antiplatelet Activity of 4-Ethoxy-isophthalamides

摘要

With the help of spatial quantitative structure-activity relationships (QSAR) contour maps obtained by comparative molecular field analysis (CoMFA), a series of 4-ethoxyisophthalamide compounds were prepared and some of them with higher activity were found. This paper continues the structural design, preparation, spectral confirmation of thirteen new 4-ethoxyisophthalamide compounds and completes their preliminary screening of activity in response to the following inducers: adenosine diphosphate (ADP) and collagen. Among them, when ADP was used as an inducer, compounds whose activities are higher or close to picotamide, the IC(50)value also were calculated and revealed that one compound16(IC50 : 0.26 mu mol L-1) was more than three times more active than positive control drug picotamide. Meanwhile, cytotoxic effects in vitro of compound11*and compound16on L929 cells were analyzed. The structure-activity relationship showed that when electron-withdrawing groups nitro or trifluoromethyl are introduced at themeta- orpara- position of the two side chain benzene rings, it is beneficial on the whole to the improvement of antiplatelet activity.