Structure-guided evolution of a 2-phenyl-4-carboxyquinoline chemotype into PPARα selective agonists: New leads for oculovascular conditions.

Small molecule agonism of PPARα represents a promising new avenue for the development of non-invasive treatments for oculovascular diseases like diabetic retinopathy and age-related macular degeneration. Herein we report initial structure-activity relationships for the newly identified quinoline-based PPARα agonist, Y-0452. Preliminary computational studies led to the hypothesis that carboxylic acid transposition and deconstruction of the Y-0452 quinoline system would enhance ligand-protein interactions and better complement the nature of the binding pocket.