Synthesis of Tic-d-Phe Ψ[CH2–CH2] isostere and its use in the development of melanocortin receptor agonists

Abstract The first synthesis of Tic- d -Phe Ψ[CH 2 –CH 2 ] isostere is described, which features diastereoselective alkylation of the tricyclic lactam 14 . The use of this novel dipeptide isostere in the development of melanocortin agonists has been demonstrated by the synthesis of peptidomimetic 7 and non-peptidic ligand 27 . Both compounds displayed significant binding and agonist potency at the MC4R.