含噻二唑环噻吩并[2,3-d]嘧啶类含氟衍生物的合成及抗肿瘤活性

Synthesis and Antitumor Activity of Fluorinated Thieno-[2,3-d]pyrimidine Derivatives Containing 1,3,4-Thiadiazole

通过2-氨基-3-氰基噻吩与三氟乙酸、三氯氧磷反应＂一锅法＂制得2-三氟甲基-4-氯噻吩并[2,3-d]嘧啶,收率为60%,再与2-氨基-5-（取代苄硫基）-1,3,4-噻二唑发生芳香族亲核取代反应合成10个含噻二唑环噻吩并[2,3-d]嘧啶类含氟衍生物,收率为64%-75%。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,并采用MTT法对其进行初步的体外抗肿瘤活性筛选。结果表明,化合物Ⅳc和Ⅳf对Hep G2和BGC-823细胞的抑制活性高于对照样吉非替尼。

Ten fluorinated thieno [ 2,3-d ] pyrimidine derivatives containing 1,3,4-thiadiazole were synthesized in the yields of 64% -75% by SNAr reaction of 2-amino-5-（ substituted benzylthio）- 1,3, 4-thiadiazoles with 4-chloro-2-trifluoromethylthieno [ 2,3-d ] pyrimidine, which were efficiently prepared from 2-aminothiophene-3-carbonitrile, trifluoroacetic acid and phosphorus oxychloride by one-pot procedure in 60% yield. The structures of the products were confirmed by IR,^1HNMR, MS and elemental analysis. The in vitro antitumor activity of these compounds against HepG2 and BGC - 823 cell lines was evaluated by MTF assay. The results show that compounds 1V c and IV f possess higher antitumor activity than the positive control gefitinib.