Abstract
An X-ray-guided design approach led to the identification of a novel, balanced class of alpha-ethoxy-phenylpropionic acid-derived dual PPARalpha/gamma agonists. The series shows a wide range of PPARalpha/gamma ratios within a rather narrow structural space. Advanced compounds possess favorable physicochemical and pharmacokinetic profiles and show a high efficacy in T2D and dyslipidemia animal models.
MeSH terms
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Animals
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Computer Simulation
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Crystallography, X-Ray
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Diabetes Mellitus, Type 2 / drug therapy
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Drug Design
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Humans
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Hypolipidemic Agents / chemical synthesis
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Hypolipidemic Agents / chemistry*
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Hypolipidemic Agents / pharmacokinetics
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Mice
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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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Phenylpropionates / chemical synthesis
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Phenylpropionates / chemistry*
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Phenylpropionates / pharmacokinetics
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Rats
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Hypolipidemic Agents
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PPAR alpha
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PPAR gamma
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Phenylpropionates