2,4-二氨基-5-甲基-6-(取代苄基氨基)喹唑啉的合成及其生物活性

SYNTHESIS AND ACTIVITIES OF 2,4-DIAMINO 5-METHYL-6-(N-SUBSTITUTED BENZYLAMINO)-QUINAZOLINES

根据非经典叶酸拮抗剂氨基喹唑啉类的构效关系和叶酸代谢机理,设计合成了27个2,4-二氨基-5-甲基-6-(取代苄基氨基)喹唑啉(1),其中26个为未知化合物。

A series of 2,4-diamino-5-methyl-6-(substituted benzylamino)quinazolines(1)as potential folate antagonist weresynthesized.Twenty six out of all the 27 compounds havenot been reported.Condensation of 5-methyl-2,4,6-triamino-quinazoline with the substituted benzaldehydesproduced the corresponding Shiff bases,followedby reduction with NaBH_4 or PrO_2 catalytichydrogenation and subseguent formylationto form 2,4-diamino-5-methyl-6-(N-formyl-N-substituted benzylamino)quinazolines(2).2,4-Diamino-5-methyl-6-(N-nitroso-N-substi-tuted benzylamino)-(3),and 2,4-diamino-5-methyl-6-(N-methyl-N-substituted benzylami-no)quinazolines(4)were also synthesized from1.Screening with Plasmodium berghei inmice,and L 1210 leukemia cell,B 16 melanomacell in vitro showed that all compounds exhi-bited potent inhibitory effects.Among them 3had good antimalarial activities,and 4 exhibitedstronger anticacer activities than MTX.