Abstract
We have developed a new class of PPARalpha/gamma dual agonists, which show excellent agonistic activity in PPARalpha/gamma transactivation assay. In particular, (R)-9d was identified as a potent PPARalpha/gamma dual agonist with EC(50)s of 0.377 microM in PPARalpha and 0.136 microM in PPARgamma, respectively. Interestingly, the structure-activity relationship revealed that the stereochemistry of the identified PPARalpha/gamma dual agonists significantly affects their agonistic activities in PPARalpha than in PPARgamma.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Carbamates / chemical synthesis*
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Carbamates / chemistry*
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Chemistry, Pharmaceutical / methods*
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Drug Design
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Glycine / analogs & derivatives
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Glycine / chemistry
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Models, Chemical
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Models, Molecular
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Molecular Structure
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Oxazoles / chemistry
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PPAR alpha / agonists*
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PPAR alpha / metabolism
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PPAR gamma / agonists*
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PPAR gamma / metabolism
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Propionates / chemistry*
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Rosiglitazone
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Stereoisomerism
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Structure-Activity Relationship
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Thiazolidinediones / pharmacology
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Transcriptional Activation
Substances
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Carbamates
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Oxazoles
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PPAR alpha
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PPAR gamma
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Propionates
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Thiazolidinediones
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Rosiglitazone
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propionic acid
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Glycine
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muraglitazar