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Benzimidazole-2-pyrazole HIF Prolyl 4-Hydroxylase Inhibitors as Oral Erythropoietin Secretagogues.

ABSTRACT: HIF prolyl 4-hydroxylases (PHD) are a family of enzymes that mediate key physiological responses to hypoxia by modulating the levels of hypoxia inducible factor 1-? (HIF1?). Certain benzimidazole-2-pyrazole carboxylates were discovered to be PHD2 inhibitors using ligand- and structure-based methods and found to be potent, orally efficacious stimulators of erythropoietin secretion in vivo.

SUBMITTER: Rosen MD

PROVIDER: S-EPMC4007848 | biostudies-other | 2010 Dec

REPOSITORIES: biostudies-other

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Benzimidazole-2-pyrazole HIF Prolyl 4-Hydroxylase Inhibitors as Oral Erythropoietin Secretagogues.

Rosen Mark D MD Venkatesan Hariharan H Peltier Hillary M HM Bembenek Scott D SD Kanelakis Kimon C KC Zhao Lucy X LX Leonard Barry E BE Hocutt Frances M FM Wu Xiaodong X Palomino Heather L HL Brondstetter Theresa I TI Haugh Peter V PV Cagnon Laurence L Yan Wen W Liotta Lisa A LA Young Andrew A Mirzadegan Tara T Shankley Nigel P NP Barrett Terrance D TD Rabinowitz Michael H MH

ACS medicinal chemistry letters 20101005 9

HIF prolyl 4-hydroxylases (PHD) are a family of enzymes that mediate key physiological responses to hypoxia by modulating the levels of hypoxia inducible factor 1-α (HIF1α). Certain benzimidazole-2-pyrazole carboxylates were discovered to be PHD2 inhibitors using ligand- and structure-based methods and found to be potent, orally efficacious stimulators of erythropoietin secretion in vivo. ...[more]

PMID: 24900242

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