SAR evolution towards potent C-terminal carboxamide peptide inhibitors of Zika virus NS2B-NS3 protease
Zika virus (ZIKV) is a member of the Flaviviridae family that can cause neurological disorders and congenital malformations.
One of our studies featured in this publication, deals with an exploratory program aimed at identifying selective inhibitors of isoform-2 acid-sensing ion channels (ASIC-2). ASIC is a family of proton-activated ion channels widely expressed both in central and peripheral nervous system, as well as in cancer cells, and may represent a relevant target for drug discovery. Diminazene, a known ASIC inhibitor endowed with poor target specificity and negligible blood-brain barrier penetration, was used as a chemical starting point for optimization. Compound 2u was identified as the first selective and brain penetrant ASIC-2 inhibitor, as a useful tool to validate the role of ASIC-2 isoform in different type of neurodegenerative pathologies.
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