Ligands to the integrin receptor αvβ3

The vitronectin receptor alpha(v)beta(3) is a member of the integrin superfamily of membrane bound glycoprotein receptors that is responsible for cell-cell and cell-matrix interactions and shares the same beta subunit as the fibrinogen receptor alpha(IIb)beta(3) (also known as GPIlb/IIIa). Both these integrins recognise extracellular proteins that express the peptide sequence arginine-glycine-aspartic acid (RGD). Non-peptide RGD mimetics that bind with high affinity and selectivity to alpha(IIb)beta(3) were previously prepared as anti-thrombotic agents. More recently, medicinal chemistry groups have modified these non-peptide fibrinogen receptor antagonist lead structures to impart potency and integrin selectivity for alpha(v)beta(3). Numerous patent applications and issued patents have appeared throughout the last decade claiming structurally novel alpha(v)beta(3) antagonists as agents for the prevention and/or treatment of osteoporosis, cancer, diabetic retinopathy and rheumatoid arthritis. This review encompasses those issued patents and published patent applications that disclose ligands to alpha(v)beta(3).