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WANG Lei, MA Jun, GU Mengyue, DI Rongrong, LIU Yu, LAI Yisheng. Design, synthesis and biological evaluation of five-membered heterocyclopyrimidines as MTH1 inhibitors[J]. Journal of China Pharmaceutical University, 2018, 49(4): 407-412. DOI: 10.11665/j.issn.1000-5048.20180404
Citation: WANG Lei, MA Jun, GU Mengyue, DI Rongrong, LIU Yu, LAI Yisheng. Design, synthesis and biological evaluation of five-membered heterocyclopyrimidines as MTH1 inhibitors[J]. Journal of China Pharmaceutical University, 2018, 49(4): 407-412. DOI: 10.11665/j.issn.1000-5048.20180404
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Design, synthesis and biological evaluation of five-membered heterocyclopyrimidines as MTH1 inhibitors

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  • Based on the reported inhibitors TH287, 17 five-membered heterocyclopyrimidine derivatives were designed and synthesized by cyclization, scaffold hopping, bioisosterism and molecular docking technology. The bioassays determined by malachite green method demonstrated that the target compounds displayed good inhibitory activity against MTH1. Among them, the IC50 value of 7 compounds was less than 1 μmol/L, suggesting that these compounds may be candidates for further investigation.
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  • [1]
    Dominissini D,He C.Cancer:damage prevention targeted[J].Nature,2014,508(7495):191-192.
    [2]
    Warpman BU,Sanjiv K,Gad H,et al.Validation and development of MTH1 inhibitors for treatment of cancer[J].Ann Oncol,2016,27(12):2275-2283.
    [3]
    Giribaldi MG,Munoz A,Halvorsen K,et al.MTH1 expression is required for effective transformation by oncogenic HRAS[J].Oncotarget,2015,6(13):11519-11529.
    [4]
    Song WJ,Jiang P,Cai JP,et al.Expression of cytoplasmic 8-oxo-Gsn and MTH1 correlates with pathological grading in human gastric cancer[J].Asian Pac J Cancer Prev,2015,16(15):6335-6338.
    [5]
    Ma J,Gu MY,Liu Y,et al.Research advances in inhibitors of DNA repair enzyme MTH1[J].Prog Pharm Sci(药学进展),2017,41(1):140-150.
    [6]
    Kim Bo Ram,Won Ju-Eun,et al.Efficient synthesis of 4,5,6-trisubstituted-2-aminopyrimidines[J].Bull Korean Chem Soc,2009,30(9):2107-2110.
    [7]
    Gad H,Koolmeister T,Jemth AS,et al.MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool[J].Nature,2014,508(7495):215-221.
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