Structure-activity relationship and crystallographic studies on 4-hydroxypyrimidine HIF prolyl hydroxylase domain inhibitors.

The 2-oxoglutarate-dependent hypoxia inducible factor prolyl hydroxylases (PHDs) are targets for treatment of a variety of disease states including anemia. One PHD inhibitor is approved for use in the treatment of renal anemia and others are in late stage clinical trials. However, the number of reported templates for PHD inhibition is limited. We report structure-activity relationship and crystallographic studies on a promising class of 4-hydroxypyrimidine-containing PHD inhibitors.