Discovery of DS42450411 as a potent orally active hepcidin production inhibitor: Design and optimization of novel 4-aminopyrimidine derivatives.
Basic Information
ID: ALA4673215
Journal: Bioorg Med Chem Lett
Title: Discovery of DS42450411 as a potent orally active hepcidin production inhibitor: Design and optimization of novel 4-aminopyrimidine derivatives.
Authors: Fukuda T,Ishiyama T,Katagiri T,Ueda K,Muramatsu S,Hashimoto M,Aki A,Baba D,Watanabe K,Tanaka N
Abstract: Hepcidin has emerged as the central regulatory molecule in systemic iron homeostasis. The inhibition of hepcidin may be a favorable strategy for the treatment of anemia of chronic disease. Here, we have reported the design, synthesis, and structure-activity relationships (SAR) of a series of 4-aminopyrimidine compounds as inhibitors of hepcidin production. The optimization study of 1 led to the design of a potent and bioavailable inhibitor of hepcidin production, 34 (DS42450411), which showed serum hepcidin-lowering effects in a mouse model of interleukin-6-induced acute inflammation.
CiteXplore: 30217414
DOI: 10.1016/j.bmcl.2018.09.010
Patent ID: ┄