title: Highly potent and selective zwitterionic agonists of the delta-opioid receptor. Part 1.
abstract: A series of zwitterionic delta-opioid agonists, with targeted physicochemistry, as a strategy to limit potential for CNS exposure, were prepared. These agents were found to possess exquisite potency and selectivity over mu and kappa-opiate activity. Furthermore, analogue 3a was found to display restricted CNS exposure, as evidenced by its inactivity in a rodent hyperlocomotion assay of central opiate activity. Dog pharmacokinetic studies on 3a indicated encouraging oral bioavailability.
authors.affiliation: Department of Discovery Chemistry, Pfizer Global Research and Development, Sandwich, Kent, CT13 9NJ, UK. don.s.middleton@pfizer.com
authors.forename: Donald S
authors.initials: DS
authors.lastname: Middleton
authors.forename: Graham N
authors.initials: GN
authors.lastname: Maw
authors.forename: Clare
authors.initials: C
authors.lastname: Challenger
authors.forename: Alan
authors.initials: A
authors.lastname: Jessiman
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Johnson
authors.forename: William A
authors.initials: WA
authors.lastname: Million
authors.forename: Carly L
authors.initials: CL
authors.lastname: Nichols
authors.forename: Jenny A
authors.initials: JA
authors.lastname: Price
authors.forename: Michael
authors.initials: M
authors.lastname: Trevethick
mesh_terms: D000818:Animals; D004285:Dogs; D015195:Drug Design; D007211:Indoles / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D007546:Isoquinolines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D051379:Mice; D008968:Molecular Conformation; D008970:Molecular Weight; D017465:Receptors, Opioid, delta / Q000819:agonists*; D013329:Structure-Activity Relationship
chemical_list: D007211:Indoles; D007546:Isoquinolines; D017465:Receptors, Opioid, delta