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Synthesis and evaluation of new 2,6-diamino-5-hetarylpyrimidines as inhibitors of dihydrofolate reductase

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Abstract

Synthetic approaches for the preparation of 6-amino-5-hetarylpyrimidine derivatives by the ring transformation reaction of 2-hetaryl-2-(tetrahydro-2-furanyliden)acetonitriles with amidines have been developed. Some of 2,6-diamino-5-(1,3-benzothiazol-2-yl)pyrimidines were found to exhibit modest inhibitory activity against human dihydrofolate reductase. Molecular docking was performed to evaluate the binding mode of compounds of this series in the enzyme’s active site.

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Authors and Affiliations

  1. Chemistry Department, Taras Shevchenko National University of Kyiv, 12 Lva Tolstoho st., Kiev, 01601, Ukraine

    Olga V. Khilya, Demyd S. Milokhov & Yulian M. Volovenko

  2. Department of Bioorganic Mechanisms, Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine, 1 Murmanska st., Kiev, 02660, Ukraine

    Lyudmyla A. Kononets, Oleksandr L. Kobzar & Andriy I. Vovk

Authors
  1. Olga V. Khilya
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  2. Demyd S. Milokhov
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  3. Lyudmyla A. Kononets
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  4. Oleksandr L. Kobzar
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  5. Andriy I. Vovk
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  6. Yulian M. Volovenko
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Correspondence to Demyd S. Milokhov.

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Khilya, O.V., Milokhov, D.S., Kononets, L.A. et al. Synthesis and evaluation of new 2,6-diamino-5-hetarylpyrimidines as inhibitors of dihydrofolate reductase. Monatsh Chem 149, 813–822 (2018). https://doi.org/10.1007/s00706-017-2032-7

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  • DOI: https://doi.org/10.1007/s00706-017-2032-7

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