IRBM and their collaborators’ at the universities of Strasbourg and Siena have recently published a paper in the ACS Medicinal Chemistry Letters which describes their approach to the identification of a 5-dihydroxypyrimidine-6-carboxamide substructure as a privileged scaffold of a new class of HIV-1 NC inhibitors. The HIV-1 nucleocapsid (NC) protein is a target of great interest because it is essential for viral replication. A bioisosteric catechol replacement approach led to identification the 5-dihydroxypyrimidine-6-carboxamide scaffold and subsequent hit validation efforts generated optimized analogs showing improved NC inhibition and antiviral activity as well as good ADME and PK properties.
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