Synthesis and Cap-Dependent Endonuclease Inhibition of Baloxavir Derivatives

Baloxavir marboxil is a creative antiviral drug for influenza A and B viruses with novel mechanism of action. In this study, three series comprising total 21 previously unreported target compounds were designed synthesized. The drug-likeness these was evaluated by molecular docking, PAINS-Remover SwissADME. inhibitory effect affinity the on cap-dependent endonuclease activity virus evaluated. Compounds I-4, II-1~II-9 compound III-8 showed similar to baloxavir (7.45 μM) endonuclease. particular, I-4 (3.29 II-2 (1.46 strong activity. structure–activity relationship studies that inhibitive enhanced when dibenzothiepin rings substituted diphenylmethyl containing chiral-center electron-withdrawing groups, dibenzocycloheptane, dihydrodibenzo[b,e]oxepin, five-member heterocycles aryl substitution.