title: SAR and biological evaluation of 3-azabicyclo[3.1.0]hexane derivatives as μ opioid ligands.
abstract: 3-Azabicyclo[3.1.0]hexane compounds were designed as novel achiral μ opioid receptor ligands for the treatment of pruritus in dogs. In this paper, we describe the SAR of this class of opioid ligand, highlighting changes to the lead structure which led to compounds having picomolar binding affinity, selective for the μ receptor over δ and κ subtypes. Some subtleties of functional activity will also be described.
authors.affiliation: Pfizer Global Research and Development, Sandwich Laboratories, Sandwich, UK.
authors.forename: Graham
authors.initials: G
authors.lastname: Lunn
authors.forename: Lee R
authors.initials: LR
authors.lastname: Roberts
authors.forename: Stephane
authors.initials: S
authors.lastname: Content
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Critcher
authors.forename: Sara
authors.initials: S
authors.lastname: Douglas
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Fenwick
authors.forename: David M
authors.initials: DM
authors.lastname: Gethin
authors.forename: Graham
authors.initials: G
authors.lastname: Goodwin
authors.forename: David
authors.initials: D
authors.lastname: Greenway
authors.forename: Sean
authors.initials: S
authors.lastname: Greenwood
authors.forename: Kim
authors.initials: K
authors.lastname: Hall
authors.forename: Martin
authors.initials: M
authors.lastname: Thomas
authors.forename: Stephen
authors.initials: S
authors.lastname: Thompson
authors.forename: David
authors.initials: D
authors.lastname: Williams
authors.forename: Gavin
authors.initials: G
authors.lastname: Wood
authors.forename: Andrew
authors.initials: A
authors.lastname: Wylie
mesh_terms: D000818:Animals; D000982:Antipruritics / Q000138:chemical synthesis* / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000494:pharmacology; D004285:Dogs; D006168:Guinea Pigs; D006586:Hexanes / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008024:Ligands; D011537:Pruritus / Q000188:drug therapy* / Q000378:metabolism; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C532932:3-azabicyclo(3.1.0)hexane; D000982:Antipruritics; D019086:Bridged Bicyclo Compounds, Heterocyclic; D006586:Hexanes; D008024:Ligands; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu