Evaluation of 3-carbamoylpropanoic acid analogs as inhibitors of human hypoxia-inducible factor (HIF) prolyl hydroxylase domain enzymes
Chong MP., Toh LR., Tumber A., Chan YY., Chan MC., Abboud MI., Schofield CJ., Yeoh KK.
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature. There is current interest in developing human hypoxia-inducible factor (HIF) prolyl hydroxylase domain (PHD) inhibitors for the treatment of anemia and other hypoxia-related diseases. We describe the synthesis of 3-carbamoylpropanoic acid derivatives and their evaluation as human PHD-2 inhibitors. MS assays indicated that derivatives with a 3-carbamoylpropanoic acids-containing benzoxazole moiety are inhibitors of PHD-2 with IC50 values of 2.24 μM and 1.32 μM, respectively. However, neither the acids nor their respective ethyl esters were observed to upregulate HIF-1α levels in cells.