9-Arylpurines as a novel class of enterovirus inhibitors

Here we report on a novel class of enterovirus inhibitors that can be structurally described as 9-arylpurines. These compounds elicit activity against a variety of enteroviruses in the low microM range including Coxsackie virus A16, A21, A24, Coxsackie virus B3, and echovirus 9. Structure-activity relationship (SAR) studies indicate that a chlorine or bromine atom is required at position 6 of the purine ring for antiviral activity. The most selective compounds in this series inhibited Coxsackie virus B3 replication in a dose-dependent manner with EC(50) values around 5-8 microM. No toxicity on different cell lines was observed at concentrations up to 250 microM. Moreover, no cross-resistance to TBZE-029 and TTP-8307 CVB3 resistant strains was detected.status: publishe

9-Arylpurines as a Novel Class of Enterovirus Inhibitors

Here wereporton a novel class ofenterovirus inhibitors thatcan bestructurallydescribedas9-arylpurines. These compounds elicit activityagainst a varietyof enteroviruse s in the low μMrange including Coxsackie virus A16, A21, A24, Coxsackie virus B3, and echovirus 9. Structure-activity relationship(SAR) studies indicatethat achlorine orbromine atomisrequired atposition 6of the purinering for antiviralactivity. The most selective compounds in this series inhibited Coxsackie virus B3 replication in a dose-dependent manner withEC50 values around5-8μM. No toxicity ondifferent celllines wasobservedatconcentrations up to 250 μM. Moreover, no cross-resistance to TBZE-029 and TTP-8307 CVB3 resistant strains was detected.L.A. thanks the Spanish Ministerio de Educaci on y Ciencia for a FPU predoctoral fellowship. E-M.P. has a CSIC contract from the I3P programme financed by the Fondo Social Europeo (F.S.E.). We thank Marı´a Nares for excellent technical assistance. This workhas been supportedby a grant ofthe SpanishCICYT(SAF2006- 12713-C02-01) and has received the FAES FARMA SA award for young researchers in the XIV call sponsored by the Spanish Society of Medicinal Chemistry (SEQT). This work was also supportedbythe VIZIEREUFP7-Integrated Project (LSHG-CT-2004-51196).Peer reviewe