Abstract
Beginning with the weakly active lead structure 1, a new series of hPPAR agonists was developed. In vivo glucose and triglyceride lowering activity was obtained by homologation and oxamination to 3, then conversion to substituted benzisoxazoles 4 and 5. Further manipulation afforded benzofurans 6 and 7. Compound 7 was of comparable potency as a glucose and triglyceride lowering agent in insulin resistant rodents to BRL 49653.
MeSH terms
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Animals
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Blood Glucose / metabolism
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Dose-Response Relationship, Drug
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Drug Design
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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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Insulin Resistance
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Male
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Mice
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Phenylacetates / chemical synthesis*
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Phenylacetates / pharmacokinetics
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Phenylacetates / pharmacology*
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Rats
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Rats, Zucker
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Receptors, Cytoplasmic and Nuclear / agonists*
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Rosiglitazone
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Thiazoles / pharmacology
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Thiazolidinediones*
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Transcription Factors / agonists*
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Triglycerides / blood
Substances
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Blood Glucose
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Hypoglycemic Agents
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Phenylacetates
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Receptors, Cytoplasmic and Nuclear
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Thiazoles
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Thiazolidinediones
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Transcription Factors
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Triglycerides
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Rosiglitazone