2,4-二氨基-5-取代苯胺基嘧啶类化合物的合成及抗菌活性

在嘧啶类化合物中,以2,4-二氨基嘧啶类化合物对二氢叶酸还原酶的抑制作用较强。甲氧苄胺嘧啶(TMP)已作为磺胺类药物及某些抗生素的抗菌增效剂广泛用于临床。为了寻找抑酶活性或对细菌选择性抑制作用比TMP更强的化合物,对2,4-二氨基-5-取代苄基嘧啶类的苯环上取代基的改造已做了大量的工作;对这类化合物抑酶活性的构效关系也进行了较多的研究。但对这类化合物中嘧啶环与苯环间的桥键次甲基的改造则报道不多。为了

SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF 2,4-DIAMINO-5-(SUBSTITUTED ANILINO) PYRIMIDINES

On the basis of bio-isosteric principle, 10 compounds of the 2,4-diamino-5-(substituted anilino) pyrimidines were synthesized by condensation of 5-bromouracil with corresponding substituted anilines, followed by chlorination with POCl_3 and amination under high pressure. The antibacterial activities of these compounds on E. coli 1515 were also reported. Compounds 111_6(x=3-OC_4H_9-n) and 111_7 (x=2,4-(CH_3)_2) showed a fair antibacterial activity. Their activities probably depend on the hydrophobicity of pyrimidine compounds. Further studies are in progress.