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

Autor: Holt-Martyn JP; Department of Chemistry , University of Oxford , Chemistry Research Laboratory , 12 Mansfield Road , Oxford , OX1 3TA , UK . Email: christopher.schofield@chem.ox.ac.uk., Tumber A; Department of Chemistry , University of Oxford , Chemistry Research Laboratory , 12 Mansfield Road , Oxford , OX1 3TA , UK . Email: christopher.schofield@chem.ox.ac.uk., Rahman MZ; Department of Chemistry , University of Oxford , Chemistry Research Laboratory , 12 Mansfield Road , Oxford , OX1 3TA , UK . Email: christopher.schofield@chem.ox.ac.uk., Lippl K; Department of Chemistry , University of Oxford , Chemistry Research Laboratory , 12 Mansfield Road , Oxford , OX1 3TA , UK . Email: christopher.schofield@chem.ox.ac.uk., Figg W Jr; Department of Chemistry , University of Oxford , Chemistry Research Laboratory , 12 Mansfield Road , Oxford , OX1 3TA , UK . Email: christopher.schofield@chem.ox.ac.uk., McDonough MA; Department of Chemistry , University of Oxford , Chemistry Research Laboratory , 12 Mansfield Road , Oxford , OX1 3TA , UK . Email: christopher.schofield@chem.ox.ac.uk., Chowdhury R; Department of Chemistry , University of Oxford , Chemistry Research Laboratory , 12 Mansfield Road , Oxford , OX1 3TA , UK . Email: christopher.schofield@chem.ox.ac.uk., Schofield CJ; Department of Chemistry , University of Oxford , Chemistry Research Laboratory , 12 Mansfield Road , Oxford , OX1 3TA , UK . Email: christopher.schofield@chem.ox.ac.uk.
Jazyk: angličtina
Zdroj: MedChemComm [Medchemcomm] 2019 Mar 01; Vol. 10 (4), pp. 500-504. Date of Electronic Publication: 2019 Mar 01 (Print Publication: 2019).
DOI: 10.1039/c8md00548f
Abstrakt: 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.
Databáze: MEDLINE