Structure-Activity Relationship and Crystallographic Studies on 4-Hydroxypyrimidine HIF Prolyl Hydroxylase Domain Inhibitors.

Authors :: Holt-Martyn JP
Chowdhury R
Tumber A
Yeh TL
Abboud MI
Lippl K
Lohans CT
Langley GW
Figg W Jr
McDonough MA
Pugh CW
Ratcliffe PJ
Schofield CJ
Source :: ChemMedChem [ChemMedChem] 2020 Feb 05; Vol. 15 (3), pp. 270-273. Date of Electronic Publication: 2019 Dec 03.
Publication Year :: 2020
Abstract: The 2-oxoglutarate-dependent hypoxia inducible factor prolyl hydroxylases (PHDs) are targets for treatment of a variety of diseases including anaemia. One PHD inhibitor is approved for use for the treatment of renal anaemia and others are in late stage clinical trials. The number of reported templates for PHD inhibition is limited. We report structure-activity relationship and crystallographic studies on a promising class of 4-hydroxypyrimidine-containing PHD inhibitors.<br /> (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Subjects :: Crystallography, X-Ray
Dose-Response Relationship, Drug
Humans
Hypoxia-Inducible Factor-Proline Dioxygenases metabolism
Models, Molecular
Molecular Structure
Prolyl-Hydroxylase Inhibitors chemistry
Pyrimidinones chemistry
Structure-Activity Relationship
Hypoxia-Inducible Factor-Proline Dioxygenases antagonists & inhibitors
Prolyl-Hydroxylase Inhibitors pharmacology
Pyrimidinones pharmacology

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