Tetrahydropyridin-4-ylpicolinoylglycines as novel and orally active prolyl hydroxylase 2 (PHD2) inhibitors for the treatment of renal anemia

In this study, we developed a new type of PHD2 inhibitors with the tetrahydropyridin-4-ylpicolinoylglycine scaffold by using a scaffold hopping strategy. Among them, compound 25 showed potent inhibition toward PHD2 with an IC50 of 6.55 ± 0.41 nM. Furthermore, compound 25 upregulated reticulocytes in C57BL/6 mice. The subacute toxicological assay demonstrated 25 has no obvious toxicity in vivo. Overall, compound 25 is a promising candidate for the treatment of renal anemia.PMID:35675755 | DOI:10.1016/j.ejmech.2022.114479
Source: European Journal of Medicinal Chemistry - Category: Chemistry Authors: Source Type: research
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