Design and synthesis of substituted pyridine derivatives as HIF-1α prolyl hydroxylase inhibitors

Structure-guided de novo drug design led to the identification of a novel series of substituted pyridine derivatives as HIF-1 alpha prolyl hydroxylase inhibitors. Pyridine carboxyamide derivatives bearing a substituted aryl group at the 5-position of the pyridine ring show appreciable activity, while constraining the side chain by placing a pyrazole carboxylic acid generated a potent lead series with consistent activity against EGLN-1. (c) 2006 Elsevier Ltd. All rights reserved.