Betti reaction enables efficient synthesis of 8-hydroxyquinoline inhibitors of 2-oxoglutarate oxygenases

There is interest in developing potent, selective, and cell-permeable inhibitors of human ferrous iron and 2-oxoglutarate (2OG) oxygenases for use in functional and target validation studies. The 3-component Betti reaction enables efficient one-step C-7 functionalisation of modified 8-hydroxyquinoli...

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Bibliographic Details
Published in:Chemical communications (Cambridge, England) England), 2015-01, Vol.51 (84), p.15458-15461
Main Authors: Thinnes, C C, Tumber, A, Yapp, C, Scozzafava, G, Yeh, T, Chan, M C, Tran, T A, Hsu, K, Tarhonskaya, H, Walport, L J, Wilkins, S E, Martinez, E D, Müller, S, Pugh, C W, Ratcliffe, P J, Brennan, P E, Kawamura, A, Schofield, C J
Format: Article
Language:English
Subjects:
Dose-Response Relationship, Drug
Enzyme Inhibitors - chemical synthesis
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - pharmacology
Histones
Human
Humans
Inhibitors
Iron
Models, Molecular
Molecular Structure
Oxygenases - antagonists & inhibitors
Oxygenases - metabolism
Oxyquinoline - chemical synthesis
Oxyquinoline - chemistry
Oxyquinoline - pharmacology
Structure-Activity Relationship
Synthesis (chemistry)
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Summary:There is interest in developing potent, selective, and cell-permeable inhibitors of human ferrous iron and 2-oxoglutarate (2OG) oxygenases for use in functional and target validation studies. The 3-component Betti reaction enables efficient one-step C-7 functionalisation of modified 8-hydroxyquinolines (8HQs) to produce cell-active inhibitors of KDM4 histone demethylases and other 2OG oxygenases; the work exemplifies how a template-based metallo-enzyme inhibitor approach can be used to give biologically active compounds.
ISSN:1359-7345
1364-548X
DOI:10.1039/c5cc06095h