Nowadays, there is a strong drive to explore new areas of chemical space in search of innovative ways to bind and modulate challenging biological targets. At IRBM our peptide chemistry team has extensive expertise in peptide and macrocyclic drug discovery in various therapeutic areas.
Dihydroxypyrimidine Scaffold to Target HIV‑1 Nucleocapsid Protein
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.