Studies on spiro[4.5]decanone prolyl hydroxylase domain inhibitors

The 2-oxoglutarate (2OG) dependent hypoxia inducible factor (HIF) prolyl hydroxylases (PHDs) are targets for treatment of anaemia and other ischaemia related diseases. PHD inhibitors are in clinical trials; however, the number of reported templates for PHD inhibition is limited. We report structure–...

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Detalles Bibliográficos
Autores principales: Holt-Martyn, James P., Tumber, Anthony, Rahman, Mohammed Z., Lippl, Kerstin, Figg, William, McDonough, Michael A., Chowdhury, Rasheduzzaman, Schofield, Christopher J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2019
Materias:
Chemistry
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6482412/
https://www.ncbi.nlm.nih.gov/pubmed/31057728
http://dx.doi.org/10.1039/c8md00548f
Descripción
Sumario:The 2-oxoglutarate (2OG) dependent hypoxia inducible factor (HIF) prolyl hydroxylases (PHDs) are targets for treatment of anaemia and other ischaemia related diseases. PHD inhibitors are in clinical trials; however, the number of reported templates for PHD inhibition is limited. We report structure–activity relationship and crystallographic studies on spiro[4.5]decanone containing PHD inhibitors. Together with other studies, our results reveal spiro[4.5]decanones as useful templates for generation of potent and selective 2OG oxygenase inhibitors.

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