Targeted Synthesis of New 5-Phenyl-2-[(E)-Styryl]-1H-Pyrimidin-6-One Derivatives and Their Inhibitory Activity Toward SARS-CoV-2 Major (MPRO) and Papain-Like Proteases (PLPRO)

The use of the 5-phenyl-1 H -pyrimidin-6-one scaffold in the search for biologically active compounds with antiviral activity based on the pyrimidin-4-one core present in endogenous substances and drugs was substantiated. The molecular activity and pharmacokinetic descriptors for styryl derivatives...

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Bibliographic Details
Published in:Pharmaceutical chemistry journal 2023-11, Vol.57 (8), p.1189-1196
Main Authors: Rozhkova, A. S., Kodonidi, I. P., Anenko, D. S., Kirik, S. D., Pozdnyakov, D. I., Filippova, V. P., Vdovenko-Martynova, N. N.
Format: Article
Language:English
Subjects:
Medicine
Organic Chemistry
Pharmacology/Toxicology
Pharmacy
Search for New Drugs
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Summary:The use of the 5-phenyl-1 H -pyrimidin-6-one scaffold in the search for biologically active compounds with antiviral activity based on the pyrimidin-4-one core present in endogenous substances and drugs was substantiated. The molecular activity and pharmacokinetic descriptors for styryl derivatives of N -substituted 5-phenyl-1 H -pyrimidin-6-one were predicted in silico via the SwissADME web service. The lack of crystallographic data and information about the tautomeric form of 2,4-dimethyl-5-phenyl-1 H -pyrimidin-6-one necessitated the measurement and analysis of x-ray diffraction patterns of the starting substance to explain the reactivity in the styrylation reaction. New derivatives of 5-phenyl-2-[( E )-styryl]-1 H -pyrimidin-6-one were synthesized. Studies of their inhibitory activity toward SARS-CoV-2 major (Mpro) and papain-like proteases (PLpro) revealed their marked antiviral activity.
ISSN:0091-150X
1573-9031
DOI:10.1007/s11094-024-03025-0