Discovery of antivirally active inhibitors of adaptor protein-2 associated kinase 1 based on various bicyclic heteroaromatic scaffolds derived from a 7-azaindole analogue.

ABSTRACT: Adaptor protein-2 associated kinase 1 (AAK1) has been proposed as a promising host target for the development of broad-spectrum antiviral agents. Different regioisomers, as well as scaffolds that were not explored before for their AAK1 affinity, were prepared that were derived from a known and potent 7-azaindole-based AAK1 inhibitor. This effort led to the discovery of various pyrrolo[2,3-b]pyridines, pyrazolo[3,4-b]pyridines and pyrazolo[3,4-d]pyrimidines with low nanomolar AAK1 binding affinity. The AAK1 data were rationalized by molecular modeling. Selected congeners displayed antiviral activity against dengue virus and Venezuelan equine encephalitis virus.

SUBMITTER: Anthonissen S 

PROVIDER: S-EPMC12756906 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature