Design, synthesis, and structure-activity relationships of piperidine and dehydropiperidine carboxylic acids as novel, potent dual PPARalpha/gamma agonists

Several series of substituted dehydropiperidine and piperidine-4-carboxylic acid analogs have been designed and synthesized as novel, potent dual PPARalpha/gamma agonists. The SAR of these series of analogs is discussed. A rare double bond migration occurred during the basic hydrolysis of the alpha,...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2008-06, Vol.18 (12), p.3545
Main Authors: Ye, Xiang-Yang, Li, Yi-Xin, Farrelly, Dennis, Flynn, Neil, Gu, Liqun, Locke, Kenneth T, Lippy, Jonathan, O'Malley, Kevin, Twamley, Celeste, Zhang, Litao, Ryono, Denis E, Zahler, Robert, Hariharan, Narayanan, Cheng, Peter T W
Format: Article
Language:English
Subjects:
Binding, Competitive - drug effects
Carboxylic Acids - chemical synthesis
Carboxylic Acids - chemistry
Carboxylic Acids - pharmacology
Dose-Response Relationship, Drug
Drug Design
Humans
Inhibitory Concentration 50
Molecular Structure
Piperidines - chemical synthesis
Piperidines - chemistry
Piperidines - pharmacology
PPAR alpha - agonists
PPAR gamma - agonists
Stereoisomerism
Structure-Activity Relationship
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Summary:Several series of substituted dehydropiperidine and piperidine-4-carboxylic acid analogs have been designed and synthesized as novel, potent dual PPARalpha/gamma agonists. The SAR of these series of analogs is discussed. A rare double bond migration occurred during the basic hydrolysis of the alpha,beta-unsaturated dehydropiperidine esters 12, and the structures of the migration products were confirmed through a series of 2D NMR experiments.
ISSN:1464-3405
DOI:10.1016/j.bmcl.2008.05.014