3,5-Disubstituted-indole-7-carboxamides as IKKβ Inhibitors: Optimization of Oral Activity via the C3 Substituent.

ABSTRACT: IκB kinase β (IKKβ or IKK2) is a key regulator of nuclear factor kappa B (NF-κB) and has received attention as a therapeutic target. Herein we report on the optimization of a series of 3,5-disubstituted-indole-7-carboxamides for oral activity. In doing so, we focused attention on potency, ligand efficiency (LE), and physicochemical properties and have identified compounds 24 and (R)-28 as having robust in vivo activity.

SUBMITTER: Kerns JK 

PROVIDER: S-EPMC6295857 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature