title: Design and synthesis of substituted pyridine derivatives as HIF-1alpha prolyl hydroxylase inhibitors.
abstract: Structure-guided de novo drug design led to the identification of a novel series of substituted pyridine derivatives as HIF-1alpha 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.
authors.affiliation: Lead Discovery, Procter and Gamble Pharmaceuticals, 8700 Mason-Montgomery Rd, Mason, OH 45040, USA. Warshakoon.nc@pg.com
authors.forename: Namal C
authors.initials: NC
authors.lastname: Warshakoon
authors.forename: Shengde
authors.initials: S
authors.lastname: Wu
authors.forename: Angelique
authors.initials: A
authors.lastname: Boyer
authors.forename: Richard
authors.initials: R
authors.lastname: Kawamoto
authors.forename: Justin
authors.initials: J
authors.lastname: Sheville
authors.forename: Ritu Tiku
authors.initials: RT
authors.lastname: Bhatt
authors.forename: Sean
authors.initials: S
authors.lastname: Renock
authors.forename: Kevin
authors.initials: K
authors.lastname: Xu
authors.forename: Matthew
authors.initials: M
authors.lastname: Pokross
authors.forename: Songtao
authors.initials: S
authors.lastname: Zhou
authors.forename: Richard
authors.initials: R
authors.lastname: Walter
authors.forename: Marlene
authors.initials: M
authors.lastname: Mekel
authors.forename: Artem G
authors.initials: AG
authors.lastname: Evdokimov
authors.forename: Stephen
authors.initials: S
authors.lastname: East
mesh_terms: D015195:Drug Design; D006801:Humans; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D011393:Procollagen-Proline Dioxygenase / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D011725:Pyridines; C490190:EGLN1 protein, human; D011393:Procollagen-Proline Dioxygenase; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases