Abstract
Novel inhibitors of TGF-β1 and activin A signalling based on a 2-aryl-4-(3-(pyridin-2-yl)-1H-pyrazol-4-yl)pyridine pharmacophore have been synthesised. Compounds containing phenyl or aromatic nitrogen heterocycle substituents inhibited both types of signalling with HEK-293T cells in culture, with a selectivity preference for TGF-β1. Synthetic compounds containing pyridin-3-yl, pyrazol-4-yl, pyrazol-1-yl or 1H-imidazoyl-1-yl substituents exhibited structural and functional attributes suitable for further investigation related to the development of more potent TGF-β inhibitors.
Copyright © 2011. Published by Elsevier Ltd.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Activins / antagonists & inhibitors*
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Activins / metabolism
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Cells, Cultured
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Dose-Response Relationship, Drug
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HEK293 Cells
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Heterocyclic Compounds / chemical synthesis
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Heterocyclic Compounds / chemistry
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Heterocyclic Compounds / pharmacology*
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Humans
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Molecular Structure
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Pyridines / chemical synthesis
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Pyridines / chemistry
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Pyridines / pharmacology*
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Signal Transduction / drug effects
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Stereoisomerism
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Structure-Activity Relationship
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Transforming Growth Factor beta1 / antagonists & inhibitors*
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Transforming Growth Factor beta1 / metabolism
Substances
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Heterocyclic Compounds
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Pyridines
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Transforming Growth Factor beta1
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activin A
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Activins