AMINO-ACIDS AND PEPTIDES - LII - DESIGN AND SYNTHESIS OF OPIOID MIMETICS CONTAINING A PYRAZINONE RING AND EXAMINATION OF THEIR OPIOID RECEPTOR-BINDING ACTIVITY

An amino group was introduced to the 3 or 6 position of a pyrazinone r ing by cyclization of dipeptidyl chloromethyl ketones, Boc-Tyr-OH was coupled with the amino function, followed bq removal of the Boc group to give pyrazinone ring-containing tyrosine derivatives. Of the variou s tyrosine derivatives prepared, eta-phenethyl-3-tyrosylaminobutyl-2(1 H)-pyrazinone exhibited strong binding to the mu-opioid receptor with a K-i value of 55.8 nM and to the delta-opioid receptor with a K-i val ue of 2165 nM and with a K(i)mu/K(i)delta value of 0.026.