New potent α_vβ₃ integrin ligands based on azabicycloalkane (γ,α)-dipeptide mimics

We have designed a new synthetic strategy for the preparation of a new class of cyclic RGD integrin ligands in which the azabicycloalkane scaffold can be envisaged as a (γ,α) dipeptide mimic. The synthesis and in vitro biological evaluation of these RGD derivatives, as well as the computational study of their conformational properties and binding modes to α_Vβ₃ integrin are described. Compound 3 has shown to be a promising candidate as α_Vβ₃ integrin antagonist able to interfere with both cell adhesion and movement on vitronectin with no evidence of cytotoxic effects.