Nonpeptide αvβ3 antagonists. Part 2: constrained glycyl amides derived from the RGD tripeptide

Abstract Mimetics of the RGD tripeptide are described that are potent, selective antagonists of the integrin receptor, α v β 3 . The use of the 5,6,7,8-tetrahydro[1,8]naphthyridine group as a potency-enhancing N-terminus is demonstrated. Two 3-substituted-3-amino-propionic acids previously contained in α IIb β 3 antagonists were utilized to enhance binding affinity and functional activity for the targeted receptor. Further affinity increases were then achieved through the use of cyclic glycyl amide bond constraints.