Conversion of carbazole carboxamide based reversible inhibitors of Bruton's tyrosine kinase (BTK) into potent, selective irreversible inhibitors in the carbazole, tetrahydrocarbazole, and a new 2,3-dimethylindole series.

•Electrophilic groups increased potency and selectivity of carbazole BTK inhibitors.•Related indole analogs retained this potency and further increased selectivity.•Irreversible inhibition was demonstrated using a dialysis assay.•Better physicochemical characteristics accompanied the improved biochemical profile.