Abstract
Anthranilic acid GW9371 was identified as a novel class of PPARdelta partial agonist through high-throughput screening. The design and synthesis of SAR analogues is described. GSK1115 and GSK7227 show potent partial agonism of the PPARdelta target genes CPT1a and PDK4 in skeletal muscle cells.
MeSH terms
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Carnitine O-Palmitoyltransferase / genetics
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Carnitine O-Palmitoyltransferase / metabolism
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Combinatorial Chemistry Techniques
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Crystallography, X-Ray
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Humans
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Molecular Structure
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PPAR delta / agonists*
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Protein Kinases / genetics
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Protein Kinases / metabolism
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Structure-Activity Relationship
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Tetrahydroisoquinolines / chemical synthesis*
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Tetrahydroisoquinolines / chemistry
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Tetrahydroisoquinolines / pharmacology*
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ortho-Aminobenzoates / chemical synthesis*
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ortho-Aminobenzoates / chemistry
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ortho-Aminobenzoates / pharmacology*
Substances
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GSK1115
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GSK7227
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GW9371
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PPAR delta
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Tetrahydroisoquinolines
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ortho-Aminobenzoates
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Carnitine O-Palmitoyltransferase
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Protein Kinases
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pyruvate dehydrogenase kinase 4