title: Synthesis and evaluation of 3-amino-6-aryl-pyridazines as selective CB(2) agonists for the treatment of inflammatory pain.
abstract: A series of 3-amino-6-aryl-pyridazines have been identified as CB(2) agonists with high efficacy and selectivity against the CB(1) receptor. Details of the investigation of structure-activity relationships (SAR) are disclosed, which led to the identification of pyridazine analogue 35, a compound with high potency in an in vivo model of inflammatory pain.
authors.affiliation: Pain and Neuroexcitability Discovery Performance Unit, Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Cold Harbour Lane, Harlow, Essex CM19 5AW, United Kingdom. robert.j.gleave@gsk.com
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Gleave
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Beswick
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Brown
authors.forename: Gerard M P
authors.initials: GM
authors.lastname: Giblin
authors.forename: Paul
authors.initials: P
authors.lastname: Goldsmith
authors.forename: Carl P
authors.initials: CP
authors.lastname: Haslam
authors.forename: William L
authors.initials: WL
authors.lastname: Mitchell
authors.forename: Neville H
authors.initials: NH
authors.lastname: Nicholson
authors.forename: Lee W
authors.initials: LW
authors.lastname: Page
authors.forename: Sadhana
authors.initials: S
authors.lastname: Patel
authors.forename: Susan
authors.initials: S
authors.lastname: Roomans
authors.forename: Brian P
authors.initials: BP
authors.lastname: Slingsby
authors.forename: Martin E
authors.initials: ME
authors.lastname: Swarbrick
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D010146:Pain / Q000188:drug therapy; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; D007546:Isoquinolines; D011724:Pyridazines; D043885:Receptor, Cannabinoid, CB2