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

含苯基吡啶/苯基嘧啶-羧酰胺基团的新型4-吗啉基-7,8-二氢-5H-硫代吡喃并[4,3-d]嘧啶衍生物的合成及生物学评价

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Abstract

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 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.

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