Synthesis and antiviral activities of quinazolinamine–coumarin conjugates toward chikungunya and hepatitis C viruses

Development of new drugs with broad-spectrum to combat RNA viruses would be beneficial to mankind but faces a great challenge. We designed and efficiently synthesized a series of quinazolin-4-amine–SCH2–coumarin conjugated compounds. Our data of the virus-cell-based assay show five new conjugates inhibit chikungunya virus with EC50 values as potent as 1.96 μM and two conjugates inhibit hepatitis C virus with EC50 values as low as 16.6 μM. These conjugates possess a xylene substituent at the C-4 amino group of quinazoline and a t-butyl substituent at the C-6’ position of coumarin. [Display omitted] •New quinazolinamine–SCH2–coumarin conjugated compounds were designed and synthesized.•Five conjugates inhibited chikungunya virus (EC50 = 1.96–13.9 μM; SI = 8.8–37.2).•Two conjugates inhibited hepatitis C virus (EC50 = 16.6, 27.9 μM; SI = 7.2, 12.2).•Two conjugates performed broad-spectrum activities against CHIKV and HCV.•The potency was affected by the substituents of quinazolin-4-amine and coumarin.