title: New series of potent delta-opioid antagonists containing the H-Dmt-Tic-NH-hexyl-NH-R motif.
abstract: Heterodimeric compounds H-Dmt-Tic-NH-hexyl-NH-R (R=Dmt, Tic, and Phe) exhibited high affinity to delta- (K(i)delta=0.13-0.89nM) and mu-opioid receptors (K(i)mu=0.38-2.81nM) with extraordinary potent delta antagonism (pA(2)=10.2-10.4). These compounds represent the prototype for a new class of structural homologues lacking mu-opioid receptor-associated agonism (IC(50)=1.6-5.8muM) based on the framework of bis-[H-Dmt-NH]-alkyl (Okada, Y.; Tsuda, Y.; Fujita, Y.; Yokoi, T.; Sasaki, Y.; Ambo, A.; Konishi, R.; Nagata, M.; Salvadori, S.; Jinsmaa, Y.; Bryant, S. D.; Lazarus, L. H. J. Med. Chem.2003, 46, 3201), which exhibited both high mu affinity and bioactivity.
authors.affiliation: The Graduate School of Food and Medicinal Sciences, Kobe Gakuin University, Nishi-ku, Kobe 651-2180, Japan.
authors.forename: Tingyou
authors.initials: T
authors.lastname: Li
authors.forename: Kimitaka
authors.initials: K
authors.lastname: Shiotani
authors.forename: Anna
authors.initials: A
authors.lastname: Miyazaki
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Fujita
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tsuda
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ambo
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Yunden
authors.initials: Y
authors.lastname: Jinsmaa
authors.forename: Ewa
authors.initials: E
authors.lastname: Marczak
authors.forename: Sharon D
authors.initials: SD
authors.lastname: Bryant
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Lazarus
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Okada
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D019281:Dimerization; D007700:Kinetics; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
chemical_list: D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu