Influence of the side chain next to C-terminal benzimidazole in opioid pseudopeptides containing the Dmt-Tic pharmacophore.
To improve the structure-activity studies of the lead delta opioid agonist H-Dmt-Tic-Asp*-Bid, we synthesized and pharmacologically characterized a series of analogues in which the side chain next to 1H-benzimidazole-2-yl (Bid) was substituted by those endowed with different chemical properties. Interesting results were obtained: (1) only Gly, Ala, and Asp resulted in delta agonism, (2) Phe yielded delta antagonism, (3) and all other residues except Glu (devoid of any activity) gave mu agonism.
Balboni
Gianfranco
G
Department of Toxicology, University of Cagliari, Cagliari, Italy. gbalboni@unica.it
Trapella
Claudio
C
Sasaki
Yusuke
Y
Ambo
Akihiro
A
Marczak
Ewa D
ED
Lazarus
Lawrence H
LH
Salvadori
Severo
S
D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D004151:Dipeptides / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D009292:Narcotic Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000378:metabolism; D013379:Substrate Specificity
D001562:Benzimidazoles; D004151:Dipeptides; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; C031000:benzimidazole