Abstract
A series of 1-substituted-3(5)-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)pyrazoles 14a-e, 15a-e, 17a-c, and 18a-d have been synthesized and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. The 6-quinolinyl pyrazole analogue 14b inhibited ALK5 phosphorylation with IC(50) value of 0.022 μM and showed 84% inhibition at 0.1 μM in a luciferase reporter assay using HaCaT cells permanently transfected with p3TP-luc reporter construct.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line
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Enzyme Assays
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Humans
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Phosphorylation / drug effects
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Protein Kinase Inhibitors / chemical synthesis*
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Protein Kinase Inhibitors / pharmacology
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Protein Serine-Threonine Kinases / metabolism
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Pyrazoles / chemical synthesis*
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Pyrazoles / pharmacology
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Receptor, Transforming Growth Factor-beta Type I
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Receptors, Transforming Growth Factor beta / antagonists & inhibitors*
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Receptors, Transforming Growth Factor beta / metabolism
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Structure-Activity Relationship
Substances
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Protein Kinase Inhibitors
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Pyrazoles
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Receptors, Transforming Growth Factor beta
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Protein Serine-Threonine Kinases
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Receptor, Transforming Growth Factor-beta Type I
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TGFBR1 protein, human