Affiliation:
1. School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, China
2. Shandong Xinhua Pharmaceutical Co., Ltd., No. 1 Lutai Avenue, Zibo 255086, China
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.
Subject
Inorganic Chemistry,Condensed Matter Physics,General Materials Science,General Chemical Engineering
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