Synthesis of pyrazinone ring-containing opioid mimetics and examination of their opioid receptor-binding activity.
Cyclization of dipeptidyl chloromethyl ketones gave 6-(4-aminobutyl)-3-carboxyethyl-5-methyl-2(1H)-pyrazinone, 3-(4-aminobutyl)-6-carboxyethyl-5-methyl-2(1H)-pyrazinone, and 3,6-bis(4-aminobutyl)-5-methyl-2(1H)-pyrazinone, which were inserted into the enkephalin sequence to give opioid mimetics. Thus, it was confirmed that a pyrazinone ring can be easily inserted into a peptide sequence in order to evaluate structural components required for biologically active peptides.
Okada
Y
Y
Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Japan. okada@pharm.kobegakuin.ac.jp
Fukumizu
A
A
Takahashi
M
M
Yokoi
T
T
Tsuda
Y
Y
Bryant
S D
SD
Lazarus
L H
LH
D002851:Chromatography, High Pressure Liquid; D003500:Cyclization; D018847:Opioid Peptides / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D011719:Pyrazines / Q000138:chemical synthesis* / Q000494:pharmacology; D011957:Receptors, Opioid / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000187:drug effects; D016339:Spectrometry, Mass, Fast Atom Bombardment
C121863:3,6-bis(4-aminobutyl)-5-methyl-2(1H)-pyrazinone; C121862:3-(4-aminobutyl)-6-carboxyethyl-5-methyl-2(1H)-pyrazinone; C121861:6-(4-aminobutyl)-3-carboxyethyl-5-methyl-2(1H)-pyrazinone; D018847:Opioid Peptides; D011719:Pyrazines; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu