Abstract
We designed and synthesized novel PPARdelta antagonists based on the crystal structure of the PPARdelta full agonist TIPP-204 bound to the PPARdelta ligand-binding domain, in combination with our nuclear receptor helix 12 folding modification hypothesis. Representative compound 3a exhibits PPARdelta-preferential antagonistic activity.
MeSH terms
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Binding Sites
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Butyrates / chemical synthesis
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Butyrates / chemistry
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Butyrates / pharmacology*
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Crystallography, X-Ray
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Drug Design
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Hydrocarbons, Fluorinated / chemical synthesis
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Hydrocarbons, Fluorinated / chemistry
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Hydrocarbons, Fluorinated / pharmacology*
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Ligands
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Models, Molecular
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Molecular Structure
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PPAR delta / antagonists & inhibitors*
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Butyrates
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Hydrocarbons, Fluorinated
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Ligands
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PPAR delta
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TIPP-204