Novel highly selective peroxisome proliferator-activated receptor δ (PPARδ) modulators with pharmacokinetic properties suitable for once-daily oral dosing

Optimization of benzamide PPARδ modulator 1 led to (E)-6-(2-((4-(furan-2-yl)-N-methylbenzamido)methyl)phenoxy)-4-methylhex-4-enoic acid (18), a potent selective PPARδ modulator with significantly improved exposure in multiple species following oral administration.