Discovery of azetidinone acids as conformationally-constrained dual PPARalpha/gamma agonists.
Article Details
- CitationCopy to clipboard
Wang W, Devasthale P, Farrelly D, Gu L, Harrity T, Cap M, Chu C, Kunselman L, Morgan N, Ponticiello R, Zebo R, Zhang L, Locke K, Lippy J, O'Malley K, Hosagrahara V, Zhang L, Kadiyala P, Chang C, Muckelbauer J, Doweyko AM, Zahler R, Ryono D, Hariharan N, Cheng PT
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. Epub 2008 Feb 7.
- PubMed ID
- 18291645 [ View in PubMed]
- 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.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Rosiglitazone Peroxisome proliferator-activated receptor alpha EC 50 (nM) >5000 N/A N/A Details Rosiglitazone Peroxisome proliferator-activated receptor alpha IC 50 (nM) >15000 N/A N/A Details Rosiglitazone Peroxisome proliferator-activated receptor gamma EC 50 (nM) 45 N/A N/A Details Rosiglitazone Peroxisome proliferator-activated receptor gamma IC 50 (nM) 43 N/A N/A Details