Synthesis of 3-heteroaryl-pyrrolo[2,3-b]pyridines as potent inhibitors of AP-2-associated protein kinase 1 (AAK1) with antiviral activity
- PMID: 39427517
- DOI: 10.1016/j.ejmech.2024.116967
Synthesis of 3-heteroaryl-pyrrolo[2,3-b]pyridines as potent inhibitors of AP-2-associated protein kinase 1 (AAK1) with antiviral activity
Abstract
Inhibition of AP-2-associated protein kinase 1 (AAK1) has been shown to be a promising avenue for the development of broad-spectrum antiviral agents. On a previously described AAK1 inhibitor based on a pyrrolo[2,3-b]pyridine scaffold, the concept of isosterism was applied, by replacing a carboxamide linker by various five-membered heterocycles. It led to the discovery of a novel series of AAK1 inhibitors with IC50 values in the low nM range, that also displayed antiviral activity against the dengue virus and Venezuelan equine encephalitis virus.
Keywords: 7-Azaindole; Adaptor-associated kinase 1; Antivirals; pyrrolo[2-3-b]pyridine.
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Conflict of interest statement
Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Steven De Jonghe and Shirit Einav reports financial support was provided by US Department of Defense. Steven De Jonghe and Shirit Einav reports financial support was provided by Defense Threat Reduction Agency. Wim Dehaen reports equipment, drugs, or supplies was provided by Hercules Foundation of the Flemish Government. Wim Dehaen reports equipment, drugs, or supplies was provided by FWO-Vlaanderen. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.