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

  • Bioorg Med Chem Lett. 2008 Jun 15;18(12):3545-50. doi: 10.1016/j.bmcl.2008.05.014.
Xiang-Yang Ye  1 ,  Yi-Xin Li ,  Dennis Farrelly ,  Neil Flynn ,  Liqun Gu ,  Kenneth T Locke ,  Jonathan Lippy ,  Kevin O'Malley ,  Celeste Twamley ,  Litao Zhang ,  Denis E Ryono ,  Robert Zahler ,  Narayanan Hariharan ,  Peter T W Cheng
Affiliations
  • 1. Metabolic Diseases Chemistry, Bristol-Myers Squibb R&D, PO Box 5400, Princeton, NJ 08543-5400, USA. [email protected]
PMID: 18511276 DOI: 10.1016/j.bmcl.2008.05.014
Abstract

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.