- Thienopyrimidinone compound and use thereof
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The invention belongs to the field of chemical medicines and specifically relates to a thienopyrimidinone compound. The thienopyrimidinone compound has a structural formula shown in the description. The novel thienopyrimidinone compound can produce good inhibition effects on Tankyrase, has no obvious toxicity, can obviously inhibit the proliferation of tumor cells after STF3A cell treatment basedon the compound, has the good medicinal potential and provides a novel potential choice for clinical medication. The novel thienopyrimidinone compound can improve the expression level of an axin in the wnt signal pathway, induce the degradation of beta-catenin, thereby inhibiting the proliferation of tumor cells, can be used as a clinical prodrug candidate compound for various tumor cells and hasfurther research and development potential. A preparation method of the thienopyrimidinone compound can produce the compound with a high yield and high biological activity. The thienopyrimidinone compound has significant drug properties and has broad market prospects.
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Paragraph 0152; 0156; 0158; 0166-0169
(2019/01/20)
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- OXAZOLIDINONE COMPOUNDS AND DERIVATIVES THEREOF
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Compounds of Formula (I) and Formula (II) are useful inhibitors of tankyrase. Compounds of Formula (I) and Formula (II) have the following structure: where the definitions of the variables are provided herein.
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- Discovery of novel, induced-pocket binding oxazolidinones as potent, selective, and orally bioavailable tankyrase inhibitors
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Tankyrase (TNKS) is a poly-ADP-ribosylating protein (PARP) whose activity suppresses cellular axin protein levels and elevates β-catenin concentrations, resulting in increased oncogene expression. The inhibition of tankyrase (TNKS1 and 2) may reduce the levels of β-catenin-mediated transcription and inhibit tumorigenesis. Compound 1 is a previously described moderately potent tankyrase inhibitor that suffers from poor pharmacokinetic properties. Herein, we describe the utilization of structure-based design and molecular modeling toward novel, potent, and selective tankyrase inhibitors with improved pharmacokinetic properties (39, 40).
- Bregman, Howard,Chakka, Nagasree,Guzman-Perez, Angel,Gunaydin, Hakan,Gu, Yan,Huang, Xin,Berry, Virginia,Liu, Jingzhou,Teffera, Yohannes,Huang, Liyue,Egge, Bryan,Mullady, Erin L.,Schneider, Steve,Andrews, Paul S.,Mishra, Ankita,Newcomb, John,Serafino, Randy,Strathdee, Craig A.,Turci, Susan M.,Wilson, Cindy,Dimauro, Erin F.
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p. 4320 - 4342
(2013/07/19)
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