Abstract
Modulation of PPAR activities represents an attractive approach for the treatment of diabetes with associated cardiovascular complications. The indanylacetic acid structural motif has proven useful in the generation of potent and tunable PPAR ligands. Modification of the substituents on the linker and the heterocycle tail group allowed for the modulation of the selectivity at the different receptor subtypes. Compound 33 was evaluated in vivo, where it displayed the desired reduction of glucose levels and increase in HDL levels in various animal models.
MeSH terms
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Acetates / chemical synthesis*
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Acetates / pharmacology*
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Animals
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Area Under Curve
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Blood Glucose / metabolism
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Cells, Cultured
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Cholesterol / blood
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Diabetes Mellitus, Experimental / drug therapy
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Diabetes Mellitus, Experimental / genetics
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Dose-Response Relationship, Drug
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Humans
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Hydrolysis
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Hypoglycemic Agents / chemical synthesis*
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Hypoglycemic Agents / pharmacokinetics
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Hypoglycemic Agents / pharmacology*
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Indans / chemical synthesis*
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Indans / pharmacology*
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Indicators and Reagents
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Lipoproteins, HDL / blood
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Mice
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PPAR alpha / agonists*
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PPAR delta / agonists*
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PPAR gamma / agonists*
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Rats
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Rats, Zucker
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Rosiglitazone
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Structure-Activity Relationship
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Thiazolidinediones / therapeutic use
Substances
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Acetates
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Blood Glucose
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Hypoglycemic Agents
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Indans
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Indicators and Reagents
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Lipoproteins, HDL
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PPAR alpha
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PPAR delta
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PPAR gamma
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Thiazolidinediones
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Rosiglitazone
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Cholesterol