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

Publication Type:

Journal Article

Authors:

Rosen, Mark D; Venkatesan, Hariharan; Peltier, Hillary M; Bembenek, Scott D; Kanelakis, Kimon C; Zhao, Lucy X; Leonard, Barry E; Hocutt, Frances M; Wu, Xiaodong; Palomino, Heather L; Brondstetter, Theresa I; Haugh, Peter V; Cagnon, Laurence; Yan, Wen; Liotta, Lisa A; Young, Andrew; Mirzadegan, Tara; Shankley, Nigel P; Barrett, Terrance D; Rabinowitz, Michael H

Source:

ACS Med Chem Lett, Volume 1, Issue 9, p.526-9 (2010)

Abstract:

<p>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. </p>