Amino acids and peptides. LVI. Synthesis of pyrazinone ring-containing opioid mimetics and examination of their opioid receptor binding activity

Article abstract of DOI:10.1016/S0040-4020(99)00908-4

Cyclization of dipeptidyl chloromethyl ketones gave 6-(4-aminobutyl)-3- carboxyethyl-5-methyl-2(1H)-pyrazinone (3), 3-(4-aminobutyl)-6-carboxyethyl- 5-methyl-2(1H)-pyrazinone (6), and 3,6-bis(4-aminobutyl)-5-methyl-2(1H)- pyrazinone (15). Using above pyrazinone derivatives, three opioid mimetics were prepared (III-V). Derivatives containing 3 and 6 demonstrated weak μ and δ-opioid receptor affinities ranging from 1.6 mM to 4.1 mM while the opioid mimetic containing derivative 15 displayed higher μ-opioid receptor binding affinity (K(i)μ = 61 nM) and selectivity (K(i)μ/K(i) δ = 31).