2，4－二氨基5－氟－6－取代苄氨基喹唑啉的合成及生物活性  

SYNTHESIS AND BIOLOGICAL ACTIVITIES OF2,4- DIAMINO-5- FLUORO-6-SUBSTITUTED BENZYLAMINOQUINAZOLINES

作　　者：蒙小英[1] 刘进前[1] 张秀平[1] 陈秀华[1] 余爱珍[1] 戴祖瑞[1] 

机构地区：[1]上海医药工业研究院,上海第二军医大学

出　　处：《药学学报》1994年第4期261-267,共7页Acta Pharmaceutica Sinica

摘　　要：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Ｐｌａｓｍｏｄｉｕｍｂｅｒｇｈｅｉ抑制性治疗筛选，有６个化合物Ｉ２，４．５，６和ＩＩ５，６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Ｄｉｐｌｏｃｏｃｃｕｓｐｎｅｕｍｏｎｉａｅ活性较好。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 Diplococcuspneumoniae in in vitro tests.

关 键 词：氨基喹唑啉 合成 生物活性 

分 类 号：TQ463[化学工程—制药化工]