Abstract：
:The final stages of polio eradication are proving more difficult than the early phases, and the development of effective drugs and treatments is considered a priority; thus, the research is ongoing. A screening of our in-house chemical library against poliovirus Sabin strains led to the identification of compounds 5 and 6 as hits active at submicromolar concentrations. Derivatives of these compounds were synthesized as a preliminary structure-activity-relationship study. Among them, 7 and 11 were highly active against poliovirus Sabin 1-3. Compound 11 was also very potent against a large panel of wild and vaccine-derived polioviruses. Time-of-addition experiments suggest that 5 and 7 could be active at an early stage of viral replication, whereas 11 was active at same concentration at all stages of viral replication. A ligand-based approach was applied to find the common structural features shared by the new compounds and already-known poliovirus inhibitors.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Madia VN,Messore A,Pescatori L,Saccoliti F,Tudino V,De Leo A,Scipione L,Fiore L,Rhoden E,Manetti F,Oberste MS,Di Santo R,Costi Rdoi
10.1021/acs.jmedchem.8b01482subject
Has Abstractpub_date
2019-01-24 00:00:00pages
798-810issue
2eissn
0022-2623issn
1520-4804journal_volume
62pub_type
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