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

Mimetics of the RGD tripeptide are described that are potent, selective antagonists of the integrin receptor, αvβ3. 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 αIIbβ3 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.