Antiplatelet structure-activity relationship of tetramethylpyrazine

Tetramethylpyrazine (TMPZ) is an active component of certain plants previously found to have inhibitory effects on platelet function using both in vivo and in vitro assays(1). In this study, we examined the antiplatelet activity of structural analogues of TMPZ in order to assess structural requirements for activity. Functional requirements included nitrogen substitutions on the aromatic ring; substitutions could be either heterocyclic or ring substituted in the meta position. Enhanced antiplatelet activity was associated with increasing the number of alkyl groups on the pyrazine ring as well as increasing the length of unbranched alkyl side chains. Increased inhibition of platelet aggregation correlated with increased lipophilicity of the compounds tested. In addition, several compounds were identified which deserve further pharmacological investigation.