title: Discovery of novel hydroxy-thiazoles as HIF-alpha prolyl hydroxylase inhibitors: SAR, synthesis, and modeling evaluation.
abstract: Inhibition of the PHD2 enzyme has been associated with increased red blood cell levels. From a screening hit, a series of novel hydroxyl-thiazoles were developed as potent PHD2 inhibitors.
authors.affiliation: Chemistry Research and Discovery, Amgen, Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA. ctegley@amgen.com
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Tegley
authors.forename: Vellarkad N
authors.initials: VN
authors.lastname: Viswanadhan
authors.forename: Kaustav
authors.initials: K
authors.lastname: Biswas
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Frohn
authors.forename: Tanya A N
authors.initials: TA
authors.lastname: Peterkin
authors.forename: Catherine
authors.initials: C
authors.lastname: Chang
authors.forename: Roland W
authors.initials: RW
authors.lastname: Bürli
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Dao
authors.forename: Henrike
authors.initials: H
authors.lastname: Veith
authors.forename: Norma
authors.initials: N
authors.lastname: Rogers
authors.forename: Sean C
authors.initials: SC
authors.lastname: Yoder
authors.forename: Gloria
authors.initials: G
authors.lastname: Biddlecome
authors.forename: Philip
authors.initials: P
authors.lastname: Tagari
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Allen
authors.forename: Randall W
authors.initials: RW
authors.lastname: Hungate
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D003920:Diabetes Mellitus / Q000188:drug therapy; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004912:Erythrocytes / Q000201:enzymology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000138:chemical synthesis* / Q000737:chemistry; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D008958:Models, Molecular; D009203:Myocardial Infarction / Q000188:drug therapy; D016491:Peripheral Vascular Diseases / Q000628:therapy; D020521:Stroke / Q000188:drug therapy; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D013844:Thiazoles