Registration Number
0220U104584,
0120U104978
, R & D reports
Title
Design and synthesis of new electron-deficient azoles active against viruses causing opportunistic infections
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Head
Brovarets Volodymyr S., д.х.н.
Registration Date
23-12-2020
Organization
V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine
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4,5-Disulfonyl-substituted imidazole derivatives and imidazoles with a triphenylphosphonium group in 4th position were synthesized. The starting compounds, N-chloromethylcarboxamides, were synthesized on the basis of carboxylic acid amides by their condensation with formaldehyde. The carboxamides were further reacted with sodium sulfinates or triphenylphosphine to obtain the corresponding amides of general formula RC(O)NHCH2EWG. Such condensations have been found to proceed rapidly in acetonitrile or benzene under refluxing conditions and give high yields of the expected acylaminomethylsulfones or acylaminomethylphosphonium salts, which have been converted to the corresponding imidoyl chlorides and imidoyl isothiocyanate. The reaction conditions were optimized in order to find the most suitable bases, solvents and catalysts. New synthesized imidazole derivatives with electron-accepting substituents were purified and spectrally confirmed.
Using machine learning methods and a wide range of molecular descriptors, a number of QSAR models were constructed to predict the antiviral activity of imidazole derivatives against human cytomegalovirus and varicella virus. As a result, 20 electron-deficient imidazole derivatives with potential antiviral activity were identified and proposed for further research.
The activity of the five synthesized imidazoles was studied in vitro against the following viruses: Human cytomegalovirus (HCV, strain AD169), Herpes simplex virus 1 (HSV, strain E-377), Varicella-Zoster virus (VZV, strain Ellen).
A number of enzymes and proteins were analyzed by molecular docking: pUL89 terminus protein, CK1, CK2, CDK1, CDK2, CDK5, CDK6, CDK7, CDK8, CDK9, CDK12, and CDK13, which may be involved in the replication mechanisms of Varicella-Zoster virus and Human cytomegalovirus.
Product Description
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Buldenko Vladyslav M.
Veligina Yevheniia S.
Zhirnov Viktor V.
Zyabrev Volodymyr S.
Kachaeva Maryna V.
Kobzar Oleksandr L.
Kovalishyn Vasiliy V.
Pilyo Stepan G.
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2020-12-23
