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molecules of the month

“Compound 19” (iron-binder)

HIF prolyl hydroxylase domain inhibitor

orally active in anemia model

from structure-based scaffold hop and opt.

ACS Med. Chem. Lett., Jun. 4, 2020

Mitsubishi Tanabe Pharma, Yokohama, JP

Structure of Compound 19 (iron-binder)
1 min read

“Compound 19” (iron-binder) is an oral inhibitor of the hypoxia-inducible factor (HIF) propyl hydroxylase domain (HIF-PHD), increasing HIF levels to activate EPO transcription and promote hematopoiesis for treatment of anemia. Interestingly, this compound is modeled to make a bi-dentate interaction with an iron co-factor of HIF-PHD via a pyrimidone nitrogen and a pyrazole nitrogen. The compound is bioavailable in rats (77% F) though the molecule potentially bears two negative charges at physiological pH (pyrimidone anion and carboxylate).


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