3,5-Disubstituted-Indole-7-Carboxamides: The Discovery Of A Novel Series Of Potent, Selective Inhibitors Of Ikk-Beta

The discovery and hit-to-lead exploration of a novel series of selective IKK-beta kinase inhibitors is described. The initial lead fragment 3 was identified by pharmacophore-directed virtual screening. Homology model-driven SAR exploration of the template led to potent inhibitors, such as 12, which demonstrate efficacy in cellular assays and possess encouraging developability profiles. (C) 2011 Elsevier Ltd. All rights reserved.