Biphenyls as potent vitronectin receptor antagonists. Part 2: biphenylalanine ureas

Vitronectin receptor (α Vβ 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 Vβ 3. Identified from a combinatorial library based on a biphenyl motif, 21 is a subnanomolar vitronectin receptor (α Vβ 3) antagonist. The SAR of these biphenylalanine ureas can be rationalised by computational docking studies using the X-ray structure of α Vβ 3.