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-R (HIF1R). 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.
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