含噻二唑环吡唑并[3,4-d]嘧啶类含氟衍生物的合成及抗菌活性

Synthesis and Antibacterial Activity of Fluorinated Pyrazolo[3,4-d]pyrimidine Derivatives Containing 1,3,4-Thiadiazole

摘要:

通过5-氨基-4-氰基-1-苯基-1H-吡唑与三氟乙酸、三氯氧磷反应“一锅法”制得1-苯基-6-(三氟甲基)-4-氯-1H-吡唑并[3,4-d]嘧啶，收率为61%，再与5-芳基-2-巯基-1,3,4-噻二唑发生芳香族亲核取代反应合成8种含噻二唑环吡唑并[3,4-d]嘧啶类含氟衍生物，收率在79～87%之间。目标化合物的结构经红外光谱、核磁共振氢谱、质谱与元素分析表征。并将其对两种细菌（金黄色葡萄球菌和大肠埃希菌）进行了初步的抑菌试验。结果表明，这些化合物对金黄色葡萄球菌均有抑制作用，其中化合物IVb和IVh的抑制活性相对较高。

Abstract:

Eight fluorinated pyrazolo[3,4-d]pyrimidine derivatives containing 1,3,4-thiadiazole were synthesized in the yields of 79 ~ 87% by SNAr reaction of 5-aryl-2-mercapto-1,3,4-thiadiazoles with 4-chloro-1-phenyl-6-trifluoromethyl-1H-pyrazolo[3,4-d]pyrimidine, which were efficiently prepared from 5-amino-4-cyano-1-phenyl-1H-pyrazole, trifluoroacetic acid and trichlorophosphate by one-pot procedure in 61% yield. The structures of the products were confirmed by IR, 1H NMR, MS and elemental analysis. The primary antibacterial activity of these compounds against two bacteria (Staphylococcus aureus and Escherichia coli) was screened. The results indicated that the title compounds exhibit antibacterial activity against Staphylococcus aureus, and compounds IVb and IVh have relatively good bacteriostatic effect.