Abstract
Herein we describe a series of potent and selective PPARgamma agonists with moderate PPARalpha affinity and little to no affinity for other nuclear receptors. In vivo studies in a NIDDM animal model (ZDF rat) showed that these compounds are efficacious at low doses in glucose normalization and plasma triglyceride reduction. Compound 1b (LY519818) was selected from our SAR studies to be advanced to clinical evaluation for the treatment of type II diabetes.
MeSH terms
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Animals
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Blood Glucose / metabolism
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Cinnamates / administration & dosage
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Cinnamates / chemistry
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Cinnamates / pharmacology*
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Diabetes Mellitus, Type 2 / metabolism*
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Peroxisome Proliferator-Activated Receptors / agonists*
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Rats
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Rats, Zucker
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Structure-Activity Relationship
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Triglycerides / blood
Substances
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Blood Glucose
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Cinnamates
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Peroxisome Proliferator-Activated Receptors
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Triglycerides
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cinnamic acid