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The vitronectin receptor vβ3 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 β subunit as the fibrinogen receptor IIbβ3 (also known as GPIIb/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 IIbβ3 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 vβ3. Numerous patent applications and issued patents have appeared throughout the last decade claiming structurally novel vβ3 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 applicati...

The alpha(v)beta(3) integrin is a non-covalent, heterodimeric, cell-surface protein that is expressed with varying density on numerous cell types, including osteoclasts, vascular smooth muscle cells, endothelial cells and a variety of tumour cells. Functionally, alpha(v)beta(3) mediates a diverse range of biological events including the adhesion of osteoclasts to bone matrix, smooth muscle cell migration and angiogenesis. Specifically, there has been significant attention focused on the preparation of inhibitors of alpha(v)beta(3) for use as inhibitors of bone resorption, in recognition of the medical need for improved prevention and treatment of osteoporosis. Herein, we summarise the pertinent chemistry and biological advances in the medicinal design and biological evaluation of peptide and small molecule alpha(v)beta(3) antagonists as inhibitors of bone resorption.