N-取代-O-对甲脒苯胺基羰甲基-L-酪氨酸甲酯类化合物的合成及抗血小板聚集活性

SYNTHESIS AND BIOLOGICAL ACTIVITY OF NON-PEPTIDEFIBRINOGEN RECEPTOR ANTAGONISTS(I)-N-SUBSTITUTED-O-(4-AMINOIMINOMETHYLPHENYLAMINO) CARBONYL-METHYL-L-TYROSINE METHYL ESTER

摘要: 目的：根据RGD肽及目前活性较好的非肽类纤维。0蛋白原受体拮抗剂的结构特点,设计、合成一系列有抗血小板聚集活性的化合物。方法：以酪氨酸及对硝基苯甲酸等为主要原料经多步合成，对所得化合物用比浊法测定在1×10^-6 mol.L^-1时对体外血小板聚集的抑制率。结果：合成了18个N-取代-O-对甲脒苯胺基羰甲基-L-酪氨酸甲酯类化合物(Ia～r)，均为新化合物。结论：其中10个化合物(Ia,f,g,i～m,q,r)显示一定的活性，活性最高的（Ig）抑制率达64%。

Abstract: 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.