Synthesis and Biological Evaluation of Novel 4-Morpholino-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine Derivatives Bearing Phenylpyridine/ Phenylpyrimidine-Carboxamides

Huimin Liu, Wenhui Wang, Chengyu Sun, Caolin Wang, Wufu Zhu, Pengwu Zheng
2016 Molecules  
Four series of novel 4-morpholino-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives 11a-j, 12a-j, 13a-g and 14a-g bearing phenylpyridine/phenylpyrimidine-carboxamide scaffolds were designed, synthesized and their IC 50 values against three cancer cell lines (A549, PC-3 and MCF-7) were evaluated. Eleven of the compounds showed moderate cytotoxicity activity against the cancer cell lines. Structure-activity relationships (SARs) and pharmacological results indicated that the introduction of
more » ... e introduction of phenylpyridine-carboxamide scaffold was beneficial for the activity. What's more, the oxidation of the sulfur atom in thiopyran and various types of substituents on the aryl group have different impacts on different series of compounds. Furthermore, the positions of aryl group substituents have a slight impact on the activity of the phenylpyridine-carboxamide series compounds. Herein we disclose the synthesis and antitumor activity of all the target compounds against the A549 (human lung cancer), PC-3 (human prostatic cancer) and MCF-7 (human breast cancer) cancer cell lines, and the anti-PI3Kα kinase activity of one selected compound.
doi:10.3390/molecules21111447 pmid:27809261 fatcat:sjzc5xfvofejvjxusjpijlpeei