Structure activity relationship of novel antiviral nucleosides against Enterovirus A71.

摘要: Abstract Various (North)-methanocarba adenosine derivatives, containing rigid bicyclo[3.1.0]hexane ribose substitution, were screened for activity against representative viruses, and inhibition was observed after treatment of Enterovirus A71 with a 2-chloro-N6-1-cyclopropyl-2-methylpropan-1-yl derivative (17). µM also seen when testing 17 other enteroviruses in the Picornaviridae family. Based on this hit, structural congeners 17, N6-alkyl groups 5′ modifications, synthesized tested. The structure relationship is relatively narrow, most modifications adenine or methanocarba ring reducing abolishing inhibitory potency. 4′-Truncated 31 (MRS5474), 4′-fluoromethyl 48 (MRS7704) 4′-chloromethyl 49 nucleosides displayed EC50 ~3–4 µM, achieved SI ≥10. However, analogues ribavirin N6-benzyladenosine, shown previously to have anti-EV-A71 activity, inactive. Thus, we identified as new scaffold enterovirus narrow no similarity published anti-enteroviral nucleosides.