title: Development of novel enkephalin analogues that have enhanced opioid activities at both mu and delta opioid receptors.
abstract: Enkephalin analogues with a 4-anilidopiperidine scaffold have been designed and synthesized to achieve therapeutic benefit for the treatment of pain due to mixed mu and delta opioid agonist activities. Ligand 16, in which a Dmt-substituted enkephalin-like structure was linked to the N-phenyl-N-piperidin-4-yl propionamide moiety, showed very high binding affinities (0.4 nM) at mu and delta receptors with an increased hydrophobicity (aLogP = 2.96). This novel lead compound was found to have very potent agonist activities in MVD (1.8 nM) and GPI (8.5 nM) assays.
authors.affiliation: Department of Chemistry, University of Arizona, Tucson, Arizona 85721, USA.
authors.forename: Yeon Sun
authors.initials: YS
authors.lastname: Lee
authors.forename: Ravil
authors.initials: R
authors.lastname: Petrov
authors.forename: Chad K
authors.initials: CK
authors.lastname: Park
authors.forename: Shou-wu
authors.initials: SW
authors.lastname: Ma
authors.forename: Peg
authors.initials: P
authors.lastname: Davis
authors.forename: Josephine
authors.initials: J
authors.lastname: Lai
authors.forename: Frank
authors.initials: F
authors.lastname: Porreca
authors.forename: Ruben
authors.initials: R
authors.lastname: Vardanyan
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Hruby
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004745:Enkephalins / Q000138:chemical synthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D011869:Radioligand Assay; D051381:Rats; D017465:Receptors, Opioid, delta / Q000819:agonists*; D017450:Receptors, Opioid, mu / Q000819:agonists*; D013329:Structure-Activity Relationship; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology
chemical_list: D004745:Enkephalins; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu