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ID: ALA5214949

Journal: Bioorg Med Chem Lett

Title: Synthesis and biological evaluation of (4-hydroxy-2-(substitued sulfonamido)pyrimidine-5-carbonyl)glycines as oral erythropoietin secretagogues.

Authors: Zhi S, Cai J, Wang H, Tan C, Yang Z, Dai L, Zhang T, Wang H, Li D.

Abstract: Erythropoietin (EPO) is the predominant regulating factor in erythropoiesis. Herein we describe the identification of (4-hydroxy-2-(substitued sulfonamido)pyrimidine-5-carbonyl) glycine-based oral EPO secretagogues. Most of these compounds obviously increased the EPO level in Hep3B cells by stabilizing the hypoxia-inducible factor-α (HIF-α). Furthermore, their potential inhibitory activities against HIF prolyl hydroxylase domain (PHD) revealed their function as PHD inhibitors in PHD-HIF pathway. Compound 6i, with a biphenyl substituent on the sulfonamido group, particularly increased plasma EPO level in mice and could serve as a candidate of EPO stimulating agent for anemia treatment.

CiteXplore: 36174835

DOI: 10.1016/j.bmcl.2022.129007