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 ring by cyclization of dipeptidyl chloromethyl ketones. Boc-Tyr-OH was coupled with the amino function, followed by removal of the Boc group to give pyrazinone ring-containing tyrosine derivatives. Of the various tyrosine derivatives prepared, 5-methyl-6-beta-phenethyl-3-tyrosylaminobutyl-2(1H)-pyrazinone exhibited strong binding to the mu-opioid receptor with a Ki value of 55.8 nM and to the delta-opioid receptor with a Ki value of 2165 nM and with a Ki mu/Ki delta value of 0.026.
Okada
Y
Y
Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Japan.
Tsukatani
M
M
Taguchi
H
H
Yokoi
T
T
Bryant
S D
SD
Lazarus
L H
LH
D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D015195:Drug Design; D008958:Models, Molecular; D009294:Narcotics / Q000494:pharmacology; D011719:Pyrazines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
C115273:5-methyl-6-phenethyl-3-tyrosylaminobutyl-2(1H)-pyrazinone; D000596:Amino Acids; D009294:Narcotics; D011719:Pyrazines; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D014443:Tyrosine