Studies on spiro[4.5]decanone prolyl hydroxylase domain inhibitors

James P. Holt-Martyn; Anthony Tumber; Mohammed Z. Rahman; Kerstin Lippl; William Figg; Michael A. McDonough; Rasheduzzaman Chowdhury; Christopher J. Schofield

doi:10.1039/C8MD00548F

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

James P. Holt-Martyn,^a Anthony Tumber,^a Mohammed Z. Rahman,^a Kerstin Lippl,^a William Figg, Jr,

^a Michael A. McDonough,

^a Rasheduzzaman Chowdhury

^a and Christopher J. Schofield

*^a

Author affiliations

* Corresponding authors

^a Department of Chemistry, University of Oxford, Chemistry Research Laboratory, 12 Mansfield Road, Oxford, UK
E-mail: christopher.schofield@chem.ox.ac.uk

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.

This article is part of the themed collection: Molecular Pharmacology

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DOI: https://doi.org/10.1039/C8MD00548F
Article type: Review Article
Submitted: 05 Nov 2018
Accepted: 09 Feb 2019
First published: 01 Mar 2019
This article is Open Access

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Med. Chem. Commun., 2019,10, 500-504

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Studies on spiro[4.5]decanone prolyl hydroxylase domain inhibitors

J. P. Holt-Martyn, A. Tumber, M. Z. Rahman, K. Lippl, W. Figg, M. A. McDonough, R. Chowdhury and C. J. Schofield, Med. Chem. Commun., 2019, 10, 500 DOI: 10.1039/C8MD00548F

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

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Studies on spiro[4.5]decanone prolyl hydroxylase domain inhibitors

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