Abstract
A series of aminoindane derivatives were synthesized and shown to be potent PPARalpha agonists. The compounds were obtained as racemates in 12 steps, and tested for PPARalpha activation and PPARalpha mediated induction of the HD gene. SAR was developed by variation to the core structure as shown within. Oral bioavailability was demonstrated in a Sprague-Dawley rat, while efficacy to reduce plasma triglycerides and plasma glucose was demonstrated in db/db mice.
MeSH terms
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Amino Acids / chemistry
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Animals
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Butyrates / chemical synthesis*
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Butyrates / chemistry
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Butyrates / pharmacology*
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Combinatorial Chemistry Techniques
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Drug Design
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Humans
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Indans / chemical synthesis*
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Indans / chemistry
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Indans / pharmacology*
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Mice
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Mice, Inbred Strains
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Molecular Structure
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PPAR alpha / agonists*
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Rats
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Rats, Sprague-Dawley
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Stereoisomerism
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Structure-Activity Relationship
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Urea / analogs & derivatives*
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Urea / chemical synthesis*
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Urea / chemistry
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Urea / pharmacology*
Substances
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Amino Acids
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Butyrates
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Indans
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PPAR alpha
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Urea