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Studies on spiro[4.5]decanone prolyl hydroxylase domain inhibitors.

ABSTRACT: 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.

SUBMITTER: Holt-Martyn JP

PROVIDER: S-EPMC6482412 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Studies on spiro[4.5]decanone prolyl hydroxylase domain inhibitors.

Holt-Martyn James P JP Tumber Anthony A Rahman Mohammed Z MZ Lippl Kerstin K Figg William W Figg William W McDonough Michael A MA Chowdhury Rasheduzzaman R Schofield Christopher J CJ

MedChemComm 20190301 4

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 generati ...[more]

PMID: 31057728

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