Herein, we designed and synthesized of a novel series of 7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives bearing chromone moiety (10a–j, 13a–j). All the compounds were evaluated for the IC₅₀ values against five cancer cell lines (A549, PC-3, MCF-7, Hela and HepG2). Seven of the target compounds exhibited moderate to excellent cytotoxicity. For these compounds, we tested their inhibitory activities against mTOR kinase, and four of them were tested their inhibitory activities against PI3Kα kinase in further. The results indicated that the optimized compound 10j showed excellent inhibitory activity and cytotoxicity against mTOR kinase, PI3Kα kinase and five cancer cell lines with IC₅₀ values of 1.1 μM, 0.92 μM and 8.77–14.3 μM. Structure–activity relationships (SARs) and docking studies indicated that the thiopyrano[4,3-d]pyrimidine scaffolds exerted little effect on antitumor activities of target compounds. Substitutions of chromone moiety at C-6 position with carboxyl were benefit to the antitumor activities.

在这里，我们设计并合成了一系列带有色酮部分（10a – j，13a – j）的7,8-二氢-5 H-硫代吡喃并[4,3- d ]嘧啶衍生物。对所有化合物针对五种癌细胞系（A549，PC-3，MCF-7，Hela和HepG2）的IC ₅₀值进行了评估。七种目标化合物表现出中度至优异的细胞毒性。对于这些化合物，我们测试了它们对mTOR激酶的抑制活性，其中四个进一步测试了对PI3Kα激酶的抑制活性。结果表明，优化后的化合物10j对mTOR激酶，PI3Kα激酶和5种癌细胞系表现出优异的抑制活性和细胞毒性，IC ₅₀值分别为1.1μM，0.92μM和8.77–14.3μM。结构-活性关系（SARs）和对接研究表明，硫代吡喃并[4,3- d ]嘧啶骨架对目标化合物的抗肿瘤活性影响很小。C-6位的色酮部分被羧基取代有利于其抗肿瘤活性。