Role of benzimidazole (Bid) in the delta-opioid agonist pseudopeptide H-Dmt-Tic-NH-CH(2)-Bid (UFP-502).
H-Dmt-Tic-NH-CH(2)-Bid (UFP-502) was the first delta-opioid agonist prepared from the Dmt-Tic pharmacophore. It showed interesting pharmacological properties, such as stimulation of mRNA BDNF expression and antidepression. To evaluate the importance of 1H-benzimidazol-2-yl (Bid) in the induction of delta-agonism, it was substituted by similar heterocycles: The substitution of NH(1) by O or S transforms the reference delta-agonist into delta-antagonists. Phenyl ring of benzimidazole is not important for delta-agonism; in fact 1H-imidazole-2-yl retains delta-agonist activity.
Salvadori
Severo
S
Department of Pharmaceutical Sciences and Biotechnology Center, University of Ferrara, I-44100 Ferrara, Italy.
Fiorini
Stella
S
Trapella
Claudio
C
Porreca
Frank
F
Davis
Peg
P
Sasaki
Yusuke
Y
Ambo
Akihiro
A
Marczak
Ewa D
ED
Lazarus
Lawrence H
LH
Balboni
Gianfranco
G
D000818:Animals; D001562:Benzimidazoles; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D006801:Humans; D018716:Molecular Mimicry; D018847:Opioid Peptides / Q000737:chemistry*; D012333:RNA, Messenger / Q000187:drug effects; D017465:Receptors, Opioid, delta / Q000819:agonists*; D013329:Structure-Activity Relationship; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D001562:Benzimidazoles; D019208:Brain-Derived Neurotrophic Factor; D018847:Opioid Peptides; D012333:RNA, Messenger; D017465:Receptors, Opioid, delta; C031000:benzimidazole