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

NC Warshakoon, S Wu, A Boyer, R Kawamoto…

Index: Warshakoon, Namal C.; Wu, Shengde; Boyer, Angelique; Kawamoto, Richard; Sheville, Justin; Bhatt, Ritu Tiku; Renock, Sean; Xu, Kevin; Pokross, Matthew; Zhou, Songtao; Walter, Richard; Mekel, Marlene; Evdokimov, Artem G.; East, Stephen Bioorganic and Medicinal Chemistry Letters, 2006 , vol. 16, # 21 p. 5616 - 5620

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Citation Number: 35

Abstract

Structure-guided de novo drug design led to the identification of a novel series of substituted pyridine derivatives as HIF-1α 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.