Design and synthesis of opioidmimetics containing 2′,6′-dimethyl-l-tyrosine and a pyrazinone-ring platform

3-[4′-H-Dmt-NH-(CH2)4]-6-β-phenethyl-5-methyl-2(1H)-pyrazinone 11 bound to μ-opioid receptors, Kiμ = 0.13 nM and Kiδ/Kiμ = 447, and exhibited μ-agonism (GPI IC50 = 15.9 nM) and δ-antagonism (MVD, pA2 = 6.35).