2,3-Substituted 2-azanorbornanes as polar β-turn mimetics

The design and synthesis of N-(3-indolylmethyl)-3-benzyl-2-azabicyclo[2.2.1]heptane-2-carboxamide (3) as a conformationally constrained non-peptide β-turn mimetic is described. Compound 3 is shown to mimic the Trp and Phe side chain conformation and the overall dipole moment of MEN10627 (2), a cyclic hexapeptide with a high NK-2 affinity. The tachykinin receptor affinities of 3 are evaluated and compared to those of MEN10627 and previously reported Trp-Phe mimetic 1.