Novel pyrimidine-2,4-dione-1,2,3-triazole and furo[2,3-d]pyrimidine-2-one-1,2,3-triazole hybrids as potential anti-cancer agents: Synthesis, computational and X-ray analysis and biological evaluation

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• 作者：Tomislav Gregorić^a ; Mirela Sedić^b ; ^c ; ^{msedic@biotech.uniri.hr} ; Petra Grbčić^b ; Andrea Tomljenović Paravić^b ; Sandra Kraljević Pavelić^b ; ^c ; Mario Cetina^d ; Robert Vianello^e ; ^{robert.vianello@irb.hr} ; Silvana Raić-Malić^a ; ^{sraic@fkit.hr}
• 关键词：Furo[2 ; 3-d]pyrimidine-2-one ; 5-endo-trig cyclization ; Computational chemistry ; X-ray analysis ; Sphingolipid signaling ; Wee-1 kinase
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2017
• 出版时间：5 January 2017
• 年：2017
• 卷：125
• 期：Complete
• 页码：1247-1267
• 全文大小：1917 K
• 卷排序：125

文摘

Pd/Cu-catalyzed reactions gave furo[2,3-d]pyrimidine-2-one–1,2,3-triazole hybrids. Tandem terminal alkyne dimerization and 5-endo-trig cyclization afforded 24a–37a. Precise reaction mechanisms were elucidated by the DFT computational analysis. Compound 7 did not show mitochondrial toxicity in vitro. 7 in Hep-G2 cells inhibited Wee-1 kinase and abolished sphingolipid signaling.