Abstract
A series of novel pyridine-3-propanoic acids was synthesized. A structure-activity relationship study of these compounds led to the identification of potent dual PPARalpha/gamma agonists with varied isoform selectivity. Based on the results of efficacy studies in diabetic (db/db) mice, and the desired pharmacokinetic parameters, compounds (S)-14 and (S)-19 were selected for further profiling.
MeSH terms
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Animals
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Blood Glucose / metabolism
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Body Weight / drug effects
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Cell Line, Tumor
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Diabetes Mellitus / blood
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Diabetes Mellitus / drug therapy
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Diabetes Mellitus / pathology
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Ether / chemistry
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Humans
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Hypoglycemic Agents / chemical synthesis*
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Hypoglycemic Agents / chemistry
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Hypoglycemic Agents / pharmacology*
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Hypoglycemic Agents / therapeutic use
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Mice
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Molecular Structure
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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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Pyridines / blood*
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Pyridines / chemical synthesis
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Pyridines / pharmacology*
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Pyridines / therapeutic use
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Structure-Activity Relationship
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Thiazolidinediones / chemistry
Substances
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Blood Glucose
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Hypoglycemic Agents
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PPAR alpha
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PPAR gamma
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Pyridines
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Thiazolidinediones
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thiazolidine-2,4-dione
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Ether
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pyridine