The cis-4-amino-L-proline residue as a scaffold for the synthesis of cyclic and linear endomorphin-2 analogues.

摘要: Recently, we reported synthesis and activity of a constrained cyclic analogue endomorphin-2 (EM-2: Tyr-Pro-Phe-Phe-NH(2)) related linear models containing the cis-4-amino-L-proline (cAmp) in place native Pro(2). In present article, adopted rationale is possible modulation receptor affinity cAmp EM-2 analogues by assigning different stereochemistry to Phe(3) Phe(4) residues ring. Thus, eight more with absolute configuration at chiral center aromatic positions 3 4 have been synthesized their opioid examined. The stereochemical change α-carbon atoms leads meaningful enhancement toward μ receptors respect prototype compound 9: e.g., 9a, K(i)(μ) = 63 nM, GPI (IC(50)) 480 nM; 9b, 38 330 nM.