Acyclic N-(azacycloalkyl)bisindolylmaleimides: isozyme selective inhibitors of PKCβ

The synthesis and structure–activity relationship (SAR) trends of a new class of N-(azacycloalkyl)bisindolylmaleimides 1, acyclic derivatives of staurosporine, is described. The representative compound for this series (1e) exhibits an IC50 of 40–50 nM against the human PKCβ1 and PKCβ2 isozymes and selectively inhibits the PKCβ isozymes in comparison to other PKC isozymes (α, γ, δ, , λ, and η). The series is also kinase selective for PKC in comparison to other ATP-dependent kinases. A comparison of the PKC isozyme and kinase activity of the series is made to the kinase inhibitor staurosporine.