Evaluation of 3-carbamoylpropanoic acid analogs as inhibitors of human hypoxia-inducible factor (HIF) prolyl hydroxylase domain enzymes
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. M...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Published: |
Springer Verlag
2021
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| Subjects: | |
| Online Access: | http://eprints.um.edu.my/33952/ |
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| Summary: | 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 mu M and 1.32 mu M, respectively. However, neither the acids nor their respective ethyl esters were observed to upregulate HIF-1 alpha levels in cells. |
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