Biphenyls as Potent Vitronectin Receptor Antagonists. Part 2: Biphenylalanine Ureas

Abstract Vitronectin receptor (α V β 3 ) antagonism has been implicated in a variety of disease states, like restenosis, osteoporosis and cancer. In this work, we present the development of a novel class of biphenyl vitronectin receptor antagonists. Identified from a focused combinatorial library based on para -bromo phenylalanine, these compounds show nanomolar affinity to the vitronectin receptor and display unprecedented SAR. Their binding mode can be rationalized by computational docking studies using the X-ray structure of α V β 3 .