Abstract
In this Letter we describe the design, synthesis, screening, and optimization of a new family of ADAMTS-5 inhibitors. These inhibitors display an original 1,2,4-triazole-3-thiol scaffold as a putative zinc binding-group. In vitro results are rationalized by in silico docking of the compounds in ADAMTS-5's crystal structure.
Copyright © 2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ADAM Proteins / antagonists & inhibitors*
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ADAMTS5 Protein
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Binding Sites
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Computer Simulation
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Drug Evaluation, Preclinical
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Humans
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Indicators and Reagents
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Models, Molecular
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Osteoarthritis / drug therapy
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Protease Inhibitors / chemical synthesis*
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Protease Inhibitors / chemistry
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Protease Inhibitors / pharmacology*
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Protein Binding
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Protein Conformation
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Structure-Activity Relationship
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Triazoles / chemical synthesis*
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Triazoles / chemistry
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Triazoles / pharmacology*
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X-Ray Diffraction
Substances
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Indicators and Reagents
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Protease Inhibitors
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Triazoles
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ADAM Proteins
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ADAMTS5 Protein
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ADAMTS5 protein, human