Abstract
A series of 2-benzylamino-4(5)-(6-methylpyridin-2-yl)-5(4)-([1,2,4]triazolo[1,5-a]pyridin-6-yl)thiazoles 12a-ab, 13a, 13b, and 18a-d has been synthesized and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. The N-(3-fluorobenzyl)-4-(6-methylpyridin-2-yl)-5-([1,2,4]triazolo[1,5-a]pyridin-6-yl)thiazol-2-amine (12b) inhibited ALK5 phosphorylation with an IC(50) value of 7.01 nM and showed 61% inhibition at 30 nM in a luciferase reporter assay using HaCaT cells permanently transfected with p3TP-luc reporter construct.
Copyright © 2012 Elsevier Masson SAS. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line, Transformed
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Enzyme Assays
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Genes, Reporter
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Humans
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Keratinocytes / drug effects*
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Keratinocytes / enzymology
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Luciferases
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Molecular Docking Simulation
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Phosphorylation
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Protein Kinase Inhibitors / chemistry*
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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 / chemistry*
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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 / chemistry*
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Structure-Activity Relationship
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Thiazoles / chemical synthesis*
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Thiazoles / pharmacology
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Transfection
Substances
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Protein Kinase Inhibitors
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Receptors, Transforming Growth Factor beta
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Thiazoles
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Luciferases
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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