Synthesis and Biological Evaluation of Novel 4-Morpholino-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine Derivatives Bearing Phenylpyridine/ Phenylpyrimidine-Carboxamides.
Four series of novel 4-morpholino-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives11a-j,12a-j,13a-gand14a-gbearing phenylpyridine/phenylpyrimidine- carboxamide scaffolds were designed, synthesized and their IC50values 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.
School of Perfume and Aroma Technology, Shanghai Institute of Technology, Shanghai 201418, China. szliuhm@sit.edu.cn.
Huimin
H
Liu
School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China. wenhui410@126.com.
Wenhui
W
Wang
School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China. sunchengyu0902@126.com.|Pharmacy Department, The Affiliated Hospital of Chongqing Three Gorges Medical College, Chongqing 404000, China. sunchengyu0902@126.com.
Chengyu
C
Sun
School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China. wangcllw@126.com.
Caolin
C
Wang
School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China. zhuwf@jxstnu.edu.cn.
Wufu
W
Zhu
School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China. Zhengpw@126.com.
Pengwu
P
Zheng
D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D061986:MCF-7 Cells; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D003603:Cytotoxins; D007093:Imidazoles
PI3Kα kinase; cytotoxicity activity; phenylpyridine/phenylpyrimidine carboxamides; synthesis; thiopyrano[4,3-d]pyrimidine