Abstract
A series of 2-(6-methylpyridin-2-yl)-1H-imidazoles were synthesized and evaluated for ALK5 inhibitory activity in cell-based luciferase reporter assays. The compound 4-(((1-(benzo[d][1,3]dioxol-5-yl)-2-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)methyl)amino)benzenesulfonamide (27a) exhibited slightly higher inhibition (IC50=0.24μM) than SB431542 (IC50=0.35μM), a well known potent ALK5 inhibitor. The binding mode of 27a generated by flexible docking study shows that it fits well into the site cavity of ALK5 by forming several tight interactions.
Keywords:
ALK5; Imidazole derivatives; Kinase inhibitor; Transforming growth factor β.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Benzamides / chemistry
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Benzamides / pharmacology
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Dioxoles / chemistry
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Dioxoles / pharmacology
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Humans
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Imidazoles / chemical synthesis
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Imidazoles / chemistry*
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Imidazoles / pharmacology*
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Molecular Docking Simulation
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Protein Serine-Threonine Kinases / chemistry
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Protein Serine-Threonine Kinases / metabolism
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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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Receptors, Transforming Growth Factor beta / metabolism
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Structure-Activity Relationship
Substances
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4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide
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Benzamides
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Dioxoles
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Imidazoles
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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