O-对甲脒苯氧烷基-N-取代酪氨酸甲酯的合成与抗血小板聚集活性

非肽类纤维蛋白原受体拮抗剂阻止血小板聚集的最后一步,即活化的血小板与纤维蛋白原之间的结合1,2],是一类有新作用机制的抗血栓剂,为80年代末,90年代初以来国际上抗血栓药物研究的热点。通过对纤维蛋白原及ＲＧＤ肽的结构模拟,已获得一些高效化合物,且克服了肽类化合物的某些缺点,成为这类药物的研究方向3]。前文4,5]报道了Ｏ对甲脒苯胺基羰甲基及Ｏ对甲脒苯氧乙基Ｎ取代酪氨酸甲酯类化合物的合成及其抗血小板活性,已出现了一些有意义的苗头。为了进一步考察空间臂的极性和长度对化合物活性的影响,本文合成了一系列新的化合物ＩＶａ～ｉ…

SYNTHESIS AND ANTIAGGREGATION ACTIVITY OF O-(4-AMINOIMINOMETHYLPHENYLOXY) ALKYL-N-SUBSTITUTED-L-TYROSINE METHYL ESTERS

AIM: The synthesis and antiaggregation activity of a series of compounds with p-amidinophenyl group and tyrosine methyl esters as their terminals were studied. METHODS and RESULTS: A series of O-(4-aminoiminomethylphenyloxy)alkyl-N-substituted-L-tyrosine methyl esters were prepared from 4-cyanophenol, L-tyrosine and different dihalo-alkanes. All compounds (IVa～i) were new compounds. Their in vitro activity against ADP-induced platelet aggregation were tested. The structure-activity relationships were discussed. CONCLUSION: Some of the compounds showed antiaggregation activity on platelet rich-plasma at the final concerntration of 1×10^-6 mol.L^-1. The potency of IVa～i showed that compounds with three methylene groups are better than those with four methylene groups on the same R-substituent in the above series of compounds.