title: Structure-based design, synthesis, and SAR evaluation of a new series of 8-hydroxyquinolines as HIF-1alpha prolyl hydroxylase inhibitors.
abstract: A new series of potent 8-hydroxyquinolines was designed based on the newly resolved X-ray crystal structure of EGLN-1. Both alkyl and aryl 8-hydroxyquinoline-7-carboxyamides were good HIF-1alpha prolyl hydroxylase (EGLN) inhibitors. In subsequent VEGF induction assays, these exhibited potent VEGF activity. In addition, this class of compounds did show the ability to stabilize HIF-1alpha.
authors.affiliation: Drug Discovery Division, Procter and Gamble Pharmaceuticals Inc., 8700 Mason-Montgomery Road, 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: 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: Carol
authors.initials: C
authors.lastname: Winter
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
mesh_terms: D015195:Drug Design; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D015125:Oxyquinoline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011393:Procollagen-Proline Dioxygenase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D015125:Oxyquinoline; C490190:EGLN1 protein, human; D011393:Procollagen-Proline Dioxygenase; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases