ANTIPLATELET STRUCTURE-ACTIVITY RELATIONSHIP OF TETRAMETHYLPYRAZINE

Tetramethylpyrazine (TMPZ) is an active component of certain plants pr eviously found to have inhibitory effects on platelet function using b oth in vivo and in vitro assays(1). In this study, we examined the ant iplatelet 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 e ither heterocyclic or ring substituted in the meta position. Enhanced antiplatelet activity was associated with increasing the number of alk yl groups on the pyrazine ring as well as increasing the length of unb ranched alkyl side chains. Increased inhibition of platelet aggregatio n correlated with increased lipophilicity of the compounds tested. In addition, several compounds were identified which deserve further phar macological investigation.