Enterovirus Inhibition by Hinged Aromatic Compounds with Polynuclei

The modern world has no available drugs for the treatment of enteroviruses (EV), which affect millions of people worldwide each year. The EV71 is a major causative disease for hand, foot, and mouth disease; sometimes it is associated with severe central nervous system diseases. Treatment for enteroviral infection is mainly supportive; treatment for aseptic meningitis caused by enteroviruses is also generally symptomatic. Upon the urgent request of new anti-enterovirus drugs, a series of hinged aromatic compounds with polynulei were synthesized through two different chemical pathways. Among these morpholine–furan/thiophene/pyrrole–benzene–pyrazole conjugates, three new agents exhibited inhibitory activity with EC(50) = 2.29–6.16 μM toward EV71 strain BrCr in RD cells. Their selectivity index values were reached as high as 33.4. Their structure–activity relationship was deduced that a thiophene derivative with morpholine and trifluorobenzene rings showed the greatest antiviral activity, with EC(50) = 2.29 μM.