2,4-二氨基喹唑啉和2,4-二氨基吡啶并[2,3-d]嘧啶衍生物的合成

Synthesis of 2,4-Diaminoquinazoline and 2,4-Diaminopyrido[2,3-d]pyrimidine Derivatives

以6-氯-5-氰基烟酸、3-氰基-4-氟苯甲酸、4-氰基-3-氟苯甲酸和6-氯-5氰基-2-吡啶甲酸为原料,经过酰胺化和关环两步反应合成了2,4-二氨基喹唑啉和2,4-二氨基吡啶并[2,3-d]嘧啶衍生物,该方法操作简便,除6-氯-5-氰基-2-吡啶甲酸外,其它三种酸的反应收率可达65%以上.采用氢核磁(1H NMR)、碳核磁(13C NMR)和高效液质联用(LC-MS)分析对目标产物进行了表征.采用四甲基偶氮唑盐(MTT)法考察所合成化合物的体外抗肿瘤活性测性,结果表明部分化合物对所选肿瘤细胞的增殖有一定的抑制活性,化合物4c,4d,4e和4f对人白血病细胞(K562)和人肝癌细胞(HepG2)的抑制活性强于阳性对照药5-氟尿嘧啶(5-Fu).

In this work, several 2,4-diaminoquinazoline and 2,4-diaminopyrido[2,3-d]pyrimidine derivatives were designed and synthesized by acylation reaction and ring-closure reaction, using 6-chloro-5-cyanonicotinic acid, 3-cyano-4-fluoroben- zoic acid, 4-cyano-3-fluorobenzoic acid and 6-chloro-5-cyanopicolinic acid as starting materials. This method is simple and efficient. For the used acids but 6-chloro-5-cyanopicolinic acid, the reaction yields are above 65%. The structures of terminational compounds were determined by 1H NMR, 13C NMR and LC-MS. The antitumor activities of the nitrogen mustard-linked chalcones were evaluated by an MTT assay. The results reveal that some of the title compounds exhibit potent anti-proliferative activities against selected tumor cells. Among which, compounds 4c, 4d, 4e and 4f against K562 and HepG2 were better than 5-fluorouracil.