Abstract
The synthesis of a novel series of N-(5-amino-1-(4-methoxybenzyl)-1H-pyrazol-4-yl amide derivatives 6a-o, 7a-s and their antiproliferative activities against A375P melanoma cell line were described. Most compounds showed competitive antiproliferative activities to sorafenib, the reference standard. Among them, N-(5-amino-1-(4-methoxybenzyl)-1H-pyrazol-4-yl)-5-(3-(4-chloro-3-(trifluoromethyl)phenyl) ureido)-2-methylbenzamide 7c exhibited potent activities (GI(50)=0.27 μM). Especially, 7c was found to be a potent and selective B-Raf V600E and C-Raf inhibitor (IC(50)=0.26 μM, IC(50)=0.11 μM, respectively), showing a possibility as melanoma therapeutics.
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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Amides / chemical synthesis
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Amides / chemistry*
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Amides / therapeutic use
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry*
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Antineoplastic Agents / therapeutic use
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Benzenesulfonates / chemistry
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Binding Sites
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Cell Line, Tumor
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Computer Simulation
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Humans
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Melanoma / drug therapy*
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Niacinamide / analogs & derivatives
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Phenylurea Compounds
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / chemistry*
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Protein Kinase Inhibitors / therapeutic use
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Pyrazoles / chemistry*
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Pyridines / chemistry
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Sorafenib
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Structure-Activity Relationship
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raf Kinases / antagonists & inhibitors*
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raf Kinases / metabolism
Substances
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Amides
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Antineoplastic Agents
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Benzenesulfonates
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Phenylurea Compounds
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Protein Kinase Inhibitors
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Pyrazoles
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Pyridines
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Niacinamide
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pyrazole
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Sorafenib
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raf Kinases