新型三唑并[4,5-d]嘧啶类化合物的合成及其抗血小板聚集活性  

Synthesis and Anti-platelet Aggregation Activities of Novel Triazolo[4,5-d]pyrimidin Compounds

作　　者：王兵[1,2] 杨静[3] 姜希明 刘颖[2] 刘登科[2] 王平保[2] 

机构地区：[1]天津医科大学研究生院,天津300070 [2]天津药物研究院有限公司,天津300193 [3]天津渤海职业技术学院生物与环境工程系,天津300408 [4]天津法莫西医药科技有限公司,天津300384

出　　处：《合成化学》2016年第3期185-191,197,共8页Chinese Journal of Synthetic Chemistry

基　　金：国家科技重大专项"重大新药创制"课题(2013ZX09102014)

摘　　要：以2-丙硫基-4,6-二氯-5-氨基嘧啶为原料,与伯胺类化合物(1)经取代反应制得氨基嘧啶类化合物(2);2经重氮化反应制得三氮唑类化合物(3);3与胺类化合物经亲核取代反应和水解反应合成了26个新型的三唑并[4,5-d]嘧啶类化合物(6a^6z),其结构经1H NMR和ESI-MS表征。大鼠体内抗血小板聚集模型测试结果表明:26个化合物均具有一定的抗血小板聚集活性,其中,6d,6i和6l的抗血小板聚集活性较强,抑制率分别为61.9%,69.3%和71.2%。The aminopyrimidines（ 2） were obtained via the substitution reaction of 4,6-dichloro-2-（ propylthio） pyrimidin-5-amine with primary amines. Diazotization and coupling reaction of 2 provided thiazoles（ 3）. Twenty-six novel triazolo[4,5-d]pyrimidin compounds（ 6a ~ 6z） were synthesized by the nucleophilic subsititution reaction of 3 with substituted amines and hydrolysis orderly. The structures were characterized by1 H NMR and ESI-MS. The anti-platelet aggregation activities were evaluated by platelet aggregation inhibition tests in rats. The results showed that 6a ~ 6z exhibited certain anti-platelet aggregation activities. The inhibition rates of 6d,6i and 6l were 61. 9%,69. 3% and 71. 2%,respectively.

关 键 词：三唑并[4 5-d]嘧啶 合成 抗血小板聚集活性 

分 类 号：TQ616.8[化学工程—精细化工] O626.41[理学—有机化学]