Design and synthesis of novel and potent amide linked PPARgamma/delta dual agonists.
Article Details
- CitationCopy to clipboard
Shi Q, Canada EJ, Xu Y, Warshawsky AM, Etgen GJ, Broderick CL, Clutinger CK, Irwin LA, Laurila ME, Montrose-Rafizadeh C, Oldham BA, Wang M, Winneroski LL, Xie C, York JS, Yumibe NP, Zink RW, Mantlo N
Design and synthesis of novel and potent amide linked PPARgamma/delta dual agonists.
Bioorg Med Chem Lett. 2007 Dec 15;17(24):6744-9. Epub 2007 Oct 18.
- PubMed ID
- 18029178 [ View in PubMed]
- Abstract
A series of potent amide linked PPARgamma/delta dual agonists (1a) has been discovered through rational design. In the ZDF rat model of type 2 diabetes, compound (R)-3-[4-(3-{1-[(5-chloro-1,3-dimethyl-1H-indole-2-carbonyl)-amino]-ethyl}-5-fluo ro-phenoxy)-2-ethyl-phenyl]-propionic acid (42) from this series has demonstrated glucose lowering efficacy comparable to the marketed PPARgamma agonist rosiglitazone with less weight gain.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Rosiglitazone Peroxisome proliferator-activated receptor alpha IC 50 (nM) >10000 N/A N/A Details Rosiglitazone Peroxisome proliferator-activated receptor delta IC 50 (nM) >10000 N/A N/A Details Rosiglitazone Peroxisome proliferator-activated receptor gamma EC 50 (nM) 308 N/A N/A Details Rosiglitazone Peroxisome proliferator-activated receptor gamma IC 50 (nM) 67 N/A N/A Details