2-苯基-四氢噻喃并嘧啶类化合物的合成及黄嘌呤氧化酶抑制活性

Synthesis and xanthine oxidase inhibitory activities of 2-phenyl-tetrahydrothiopyrano［4, 3-d］ pyrimidine derivatives

摘要: 以4-羟基苯甲腈为原料，经醚化、水解、酰化、加成等反应，共合成12个新型的2-苯基-四氢噻喃并嘧啶类化合物( 6a ~ 6d ， 8a ~ 8h )，并进行抑制黄嘌呤氧化酶活性测试。结果表明:化合物 8a ~ 8h (100 μmol/L)均表现出不同程度的抑酶活性，其活性明显强于化合物 6a ~ 6d ，即嘧啶环上引入羧基有利于提高抑酶活性；在化合物 8a ~ 8h 中，以嘧啶环上异丙酸取代，苯环羟基乙醚化的 8f 活性最强，IC₅₀为76.0 μmol/L。

Abstract: Twelve novel 2-phenyl -tetrahydrothiopyrano［4, 3-d］pyrimidine derivatives were synthesized from 4-hydroxy-benzonitrile by etherification, hydrolysis, acylation and addition reactions, etc. The inhibitory activities against xanthine oxidase were evaluated in vitro. Results showed that compounds 8a-8h exhibited varying inhibitory potencies on xanthine oxidase at 100 μmol/L, significantly better than those of compounds 6a-6d , indicating that carboxy-substituted pyrimidine is beneficial to the inhibitory activity. Among compounds 8a-8h , 8f with isopropionic acid-substituted pyrimidine and ethyl-substituted phenol showed the best inhibition with IC₅₀ of 76. 0 μmol/L.