Benzoyl 2-methyl indoles as selective PPARγ modulators

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.

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