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• W2901615150 abstract "We report herein the design and synthesis of a series of orally active, liver-targeted hypoxia-inducible factor prolyl hydroxylase (HIF-PHD) inhibitors for the treatment of anemia. In order to mitigate the concerns for potential systemic side effects, we pursued liver-targeted HIF-PHD inhibitors relying on uptake via organic anion transporting polypeptides (OATPs). Starting from a systemic HIF-PHD inhibitor (1), medicinal chemistry efforts directed toward reducing permeability and, at the same time, maintaining oral absorption led to the synthesis of an array of structurally diverse hydroxypyridone analogues. Compound 28a was chosen for further profiling, because of its excellent in vitro profile and liver selectivity. This compound significantly increased hemoglobin levels in rats, following chronic QD oral administration, and displayed selectivity over systemic effects." @default.
• W2901615150 created "2018-11-29" @default.
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• W2901615150 date "2018-11-13" @default.
• W2901615150 modified "2023-10-06" @default.
• W2901615150 title "Discovery of Orally Bioavailable and Liver-Targeted Hypoxia-Inducible Factor Prolyl Hydroxylase (HIF-PHD) Inhibitors for the Treatment of Anemia" @default.
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• W2901615150 doi "https://doi.org/10.1021/acsmedchemlett.8b00274" @default.
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