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

摘要:

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种含噻二唑环噻吩并[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HepG2和BGC-823细胞的抑制活性高于对照样吉非替尼。

Abstract:

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, 1H NMR, MS and elemental analysis. The in vitro antitumor activity of these compounds against HepG2 and BGC-823 cell lines was evaluated by MTT assay. The results showed that compounds IVc and IVf possess higher antitumor activity than the positive control gefitinib.