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

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 inhi...

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Published inMonatshefte für Chemie Vol. 149; no. 4; pp. 813 - 822
Main Authors Khilya, Olga V., Milokhov, Demyd S., Kononets, Lyudmyla A., Kobzar, Oleksandr L., Vovk, Andriy I., Volovenko, Yulian M.
Format Journal Article
LanguageEnglish
Published Vienna Springer Vienna 01.04.2018
Springer Nature
Springer Nature B.V
Subjects
Analytical Chemistry
Chemistry
Chemistry and Materials Science
Chemistry, Multidisciplinary
Chemistry/Food Science
Dihydrofolate reductase
Inorganic Chemistry
Molecular docking
Organic Chemistry
Original Paper
Physical Chemistry
Physical Sciences
Pyrimidines
Science & Technology
Theoretical and Computational Chemistry
Nucleophilic additions
Dihydrofolate reductase
Inhibition
Ring transformation reaction
Cyclizations
2,6-Diaminopyrimidine
DESIGN
ANTIMALARIALS
SWITCH APPROACH
2,4-DIAMINOPYRIMIDINES
PYRAZOLE
RING TRANSFORMATION REACTIONS
BIOLOGICAL EVALUATION
DUAL THYMIDYLATE SYNTHASE
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Summary: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. Graphical abstract
ISSN:0026-9247
1434-4475
DOI:10.1007/s00706-017-2032-7