Novel Phenolic Antioxidants as Multifunctional Inhibitors of Inducible VCAM-1 Expression for Use in Atherosclerosis

A series of novel phenolic compounds has been discovered as potent inhibitors of TNF-α-inducible expression of vascular cell adhesion molecule-1 (VCAM-1) with concurrent antioxidant and lipid-modulating properties. Optimization of these multifunctional agents led to the identification of 3a (AGI-1067) as a clinical candidate with demonstrated efficacies in animal models of atherosclerosis and hyperlipidemia.