Author/Authors :
John J. Acton III، نويسنده , , Regina M. Black، نويسنده , , A. Brian Jones، نويسنده , , David E. Moller، نويسنده , , Lawrence Colwell، نويسنده , , Thomas W. Doebber، نويسنده , , Karen L. MacNaul، نويسنده , , Joel Berger، نويسنده , , Harold B. Wood، نويسنده ,
Abstract :
Routine screening for human PPAR ligands yielded compounds 1 and 2, both of which were sub-micromolar hPPARγ agonists. Synthetic modifications of these leads led to a series of potent substituted 3-benzyl-2-methyl indoles, a subset of which were noted to be selective PPARγ modulators (SPPARγMs). SPPARγM 24 displayed robust anti-diabetic activity with an improved therapeutic window in comparison to a PPARγ full agonist in a rodent efficacy model.
