Synthesis and structure-activity relationships of novel IKK-β inhibitors.: Part 2:: Improvement of in vitro activity

A series of 2-amino-3-eyano-4-alkyl-6-(2-hydroxyphenyl)pyridine derivatives was synthesized and evaluated as IkappaB kinase beta (IKK-beta) inhibitors. Substitution of an aminoalkyl group for the aromatic group at the 4-position on the core pyridine ring resulted in a marked increase in both kinase enzyme and cellular potencies, and provided potent IKK-beta inhibitors with IC50 values of below 100 nM. (C) 2004 Elsevier Ltd. All rights reserved.