Abstract
The structure-activity relationships of a novel series of biaryl dihydroorotate dehydrogenase (DHODH) inhibitors related to teriflunomide are disclosed. These biaryl derivatives were the result of structure-based design and proved to be potent DHODH inhibitors which in addition showed good antiproliferative activities on peripheral blood mononuclear cells and good efficacies in vivo in the rat adjuvant-induced-arthritis model.
Copyright © 2011 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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Arthritis, Experimental / drug therapy
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Binding Sites
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Biphenyl Compounds / chemical synthesis
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Biphenyl Compounds / chemistry*
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Biphenyl Compounds / therapeutic use
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Computer Simulation
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Crotonates / chemistry*
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Dihydroorotate Dehydrogenase
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Drug Design
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / therapeutic use
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Humans
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Hydroxybutyrates
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Nitriles
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Oxidoreductases Acting on CH-CH Group Donors / antagonists & inhibitors*
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Oxidoreductases Acting on CH-CH Group Donors / metabolism
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Protein Structure, Tertiary
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Rats
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Structure-Activity Relationship
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Toluidines / chemistry*
Substances
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Biphenyl Compounds
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Crotonates
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Dihydroorotate Dehydrogenase
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Enzyme Inhibitors
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Hydroxybutyrates
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Nitriles
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Toluidines
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teriflunomide
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Oxidoreductases Acting on CH-CH Group Donors