2. Academic Validation
  3. Synthesis, molecular modeling studies and biological evaluation of fluorine substituted analogs of GW 501516

Synthesis, molecular modeling studies and biological evaluation of fluorine substituted analogs of GW 501516

  • Bioorg Med Chem. 2011 Dec 1;19(23):6982-8. doi: 10.1016/j.bmc.2011.10.020.
Calin C Ciocoiu 1,  Aina W Ravna,  Ingebrigt Sylte,  Arild C Rustan,  Trond Vidar Hansen
Affiliations

Affiliation

  • 1 School of Pharmacy, Department of Pharmaceutical Chemistry, University of Oslo, PO BOX 1068, Blindern, N-0316 Oslo, Norway.
PMID: 22051054 DOI: 10.1016/j.bmc.2011.10.020
Abstract

(±)-2-Fluoro-2-(2-methyl-4-(((4-methyl-2-(4-(trifluoromethyl)phenyl)thiazol-5-yl)methyl)thio)phenoxy)acetic acid (2a) has been prepared and subjected to biological testing against all three subtypes of the PPARs. This compound exhibited agonist effects with EC(50) values of 560 and 55 nM against PPARα and PPARδ, respectively, in a luciferase assay. Moreover, compound (±)-2a also exhibited potent ability to induce oleic acid oxidation in a human myotube cell assay with EC(50)=3.7 nM. Compound (±)-2a can be classified as a dual PPARα/δ agonist with a 10-fold higher potency against the PPARδ receptor than against the PPARα receptor. Molecular modeling studies revealed that both enantiomers of 2a bind to the PPARδ receptor with similar binding energies.

Figures