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Synthesis and Cap-Dependent Endonuclease Inhibition of Baloxavir Derivatives.
- Source :
- Crystals (2073-4352); Jul2023, Vol. 13 Issue 7, p988, 17p
- Publication Year :
- 2023
-
Abstract
- Baloxavir marboxil is a creative antiviral drug for influenza A and B viruses with a novel mechanism of action. In this study, three series comprising a total of 21 previously unreported target compounds were designed and synthesized. The drug-likeness of these compounds was evaluated by molecular docking, PAINS-Remover and SwissADME. The inhibitory effect and affinity of the compounds on the cap-dependent endonuclease activity of the influenza virus were evaluated. Compounds I-4, II-1~II-9 and compound III-8 showed similar inhibitory activity to baloxavir (7.45 μM) on the cap-dependent endonuclease. In particular, compounds I-4 (3.29 μM) and II-2 (1.46 μM) showed strong cap-dependent endonuclease inhibitory activity. The structure–activity relationship studies showed that the inhibitive effect of the compounds on endonuclease was enhanced when the dibenzothiepin rings were substituted by diphenylmethyl containing chiral-center electron-withdrawing groups, dibenzocycloheptane, dihydrodibenzo[b,e]oxepin, and five-member heterocycles containing aryl substitution. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20734352
- Volume :
- 13
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- Crystals (2073-4352)
- Publication Type :
- Academic Journal
- Accession number :
- 168598825
- Full Text :
- https://doi.org/10.3390/cryst13070988