%0 Journal Article
%T Discovery of DS44470011: An oral hypoxia-inducible factor prolyl hydroxylase inhibitor for the treatment of renal anemia.
%A Fukuda T
%A Kuribayashi T
%A Takano R
%A Sasaki K
%A Tsuji T
%A Niitsu Y
%A Ishii K
%A Hashimoto M
%A Baba D
%A Ito S
%A Tanaka N
%J Bioorg Med Chem Lett
%V 108
%N 0
%D 2024 Aug 1
%M 38754564
%F 2.94
%R 10.1016/j.bmcl.2024.129799
%X Inhibition of the hypoxia-inducible factor prolyl hydroxylase (HIF-PHD) represents a promising strategy for discovering next-generation treatments for renal anemia. We identified a pyrimidine core with HIF-PHD inhibitory activity based on scaffold hopping of FG-2216 using crystal structures of HIF-PHD2 in complex with compound. By optimizing the substituents at the 2- and 6- positions of the pyrimidine core, we discovered DS44470011, which improves the effectiveness of erythropoietin (EPO) release in cells. Oral administration of DS44470011 to cynomolgus monkeys increased plasma EPO levels.