Abstract
A structure consisting of substituted hydantoin linked to a 5-(halophenyl)furan-2-yl group via an amide bond was identified as a promising scaffold for development of low-molecular-weight therapeutic agents to treat vascular dysfunction, including ischemia/reperfusion injury. Among the compounds synthesized, 5-(3,5-dichlorophenyl)-N-{2,4-dioxo-3-[(pyridin-3-yl)methyl]imidazolidin-1-yl}-2-furamide (17) possessed the most potent inhibitory activity against Ca(2+)-induced mitochondrial swelling. The structural development, synthesis and structure-activity relationship of these compounds are described.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Calcium / chemistry*
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Calcium / metabolism
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Crystallography, X-Ray
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Cyclosporine / chemical synthesis
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Cyclosporine / chemistry
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Cyclosporine / pharmacology
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Cyclosporins / chemical synthesis
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Cyclosporins / chemistry
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Cyclosporins / pharmacology
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Dantrolene / analogs & derivatives
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Dantrolene / chemistry
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Dantrolene / pharmacology*
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Dose-Response Relationship, Drug
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HL-60 Cells
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Humans
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Mitochondria / drug effects
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Mitochondria / metabolism
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Mitochondrial Membrane Transport Proteins / antagonists & inhibitors*
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Mitochondrial Membrane Transport Proteins / metabolism
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Mitochondrial Permeability Transition Pore
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Models, Molecular
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Molecular Structure
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Molecular Weight
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Muscle Relaxation / drug effects*
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Small Molecule Libraries / chemical synthesis
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Small Molecule Libraries / chemistry
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Small Molecule Libraries / pharmacology*
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Structure-Activity Relationship
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Tumor Cells, Cultured
Substances
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Cyclosporins
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Mitochondrial Membrane Transport Proteins
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Mitochondrial Permeability Transition Pore
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Small Molecule Libraries
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Cyclosporine
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cyclosporin D
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Dantrolene
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Calcium