2,4-二氨基5-氟-6-取代苄氨基喹唑啉的合成及生物活性

本文报道2,4-二氨基-5-氟-6-取代苄氨基喹唑啉类化合物的合成及抗疟、抗肿瘤和抗菌活性,这类化合物的合成是由5-氟-2,4,6-三氨基喹唑啉(6a)与取代苯甲醛缩合成Schiff碱,然后经还原、甲酰化、亚硝化或甲基化制得。5-氟-2,4,6-三氨基喹唑啉(6a)尚未见文献报道,由5-氟-2,4-二氨基喹唑啉(4)经硝化生成异构体5a和5b分离得5a后再经还原制得。经对伯氏鼠疟原虫Plasmodium berghei抑制性治疗筛选,有6个化合物I_2,4.5,6和II_5,6以每日1mg·kg^-1,给药4天,抑制率为100%;体外抗肿瘤活性以I4最强,对L1210白血病细胞的IC₅₀为9.86×10^-4μg·mL^-1,优于氨甲蝶呤(MTX);经对18种常见菌进行体外筛选,发现对肺炎双球菌Diplococcus pneumoniae活性较好。

SYNTHESIS AND BIOLOGICAL ACTIVITIES OF 2,4-DIAMINO-5-FLUORO-6-SUBSTITUTED BENZYLAMINO QUINAZOLINES

The title compounds were synthesized by condensation of 5-fluoro- 2,4,6-triaminoquinazoline(6a) with various substituted benzaldehydes to produce the corresponding Schiffbases,followed by reduction.11 and III were obtained by formylation and nitrosation of I,respectively,IV were obtained by reduction of II. Primary screening for suppressive therapeutic effects against P. berghei mice showed that six ofthe twenty-two compounds produced 100%suppression when administered orally at dose of lmg·kg^-1.All compounds exhibited potent activity against L₁₂₁₀ cell in uitro. Among themI₄ wasmore active than MTX. A number of compounds showed moderate activities against Diplococcus pneumoniae in in vitro tests.