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.
Keywords: HIF; PHD inhibitors; Prolyl 4-hydroxylase inhibitors; anemia; epo; erythropoietin; erythropoietin stimulating agents; hypoxia inducible factor.