Synthesis and biological activity of non-peptide fibrinogen receptor antagonists(I)-N-substituted-O-(4-aminoiminomethylphenylamino) carbonylmethyl-L-tyrosine methyl ester

AIM: To design and synthesize a class of compounds with inhibitory action upon ADP-induced platelet aggregation according to both the Arg-Gly-Asp(RGD) sequence and the non-peptide fibrinogen receptor antagonists that have been reported. METHODS: Tyrosine and 4-nitrobenzoic acid were used as the major reactants to obtain the target compounds by multi-step synthesis. Turbidometric technique was used to assess the inhibitory effects in vitro at 1 × 10^-6 mol·L^-1. RESULTS: Eighteen compounds of N-substituted-O-(4-aminoiminomethylphenylamino)carbonylmethyl-L-tyrosine methyl ester were synthesized, ten (Ia, f, g, i∼m, q, r) of them showed inhibitory action at the above concentrations while Ig with inhitory rate of 64% is the most potent one. CONCLUSION: All of the eighteen compounds are new compounds, and most of them showed antiaggregation action on platelet rich-plasma.