αvβ3 Antagonists Based on a Central Thiophene Scaffold

Abstract A series of novel, highly potent α v β 3 antagonists based on a thiophene scaffold and containing an acylguanidine as an Arg-mimetic is described. A number of structural features, such as cyclic versus open guanidine and a variety of lipophilic side chains, carbamates, sulfonamides and β-amino acids were explored with respect to inhibition of α v β 3 mediated cell adhesion and selectivity versus α IIb β 3 binding. In addition, compound 19 was found to be active in the TPTX model of osteoporosis.