2. Academic Validation
  3. Discovery of azetidinone acids as conformationally-constrained dual PPARalpha/gamma agonists

Discovery of azetidinone acids as conformationally-constrained dual PPARalpha/gamma agonists

  • Bioorg Med Chem Lett. 2008 Mar 15;18(6):1939-44. doi: 10.1016/j.bmcl.2008.01.126.
Wei Wang 1,  Pratik Devasthale,  Dennis Farrelly,  Liqun Gu,  Thomas Harrity,  Michael Cap,  Cuixia Chu,  Lori Kunselman,  Nathan Morgan,  Randy Ponticiello,  Rachel Zebo,  Litao Zhang,  Kenneth Locke,  Jonathan Lippy,  Kevin O'Malley,  Vinayak Hosagrahara,  Lisa Zhang,  Pathanjali Kadiyala,  Chiehying Chang,  Jodi Muckelbauer,  Arthur M Doweyko,  Robert Zahler,  Denis Ryono,  Narayanan Hariharan,  Peter T W Cheng
Affiliations

Affiliation

  • 1 Metabolic Diseases Chemistry, Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-5400, USA.
PMID: 18291645 DOI: 10.1016/j.bmcl.2008.01.126
Abstract

A novel class of azetidinone acid-derived dual PPARalpha/gamma agonists has been synthesized for the treatment of diabetes and dyslipidemia. The preferred stereochemistry in this series for binding and functional agonist activity against both PPARalpha and PPARgamma receptors was shown to be 3S,4S. Synthesis, in vitro and in vivo activities of compounds in this series are described. A high-yielding method for N-arylation of azetidinone esters is also described.

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