Synthesis and evaluation of 3-amino-6-aryl-pyridazines as selective CB(2) agonists for the treatment of inflammatory pain.
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.
Gleave
Robert J
RJ
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
Beswick
Paul J
PJ
Brown
Andrew J
AJ
Giblin
Gerard M P
GM
Goldsmith
Paul
P
Haslam
Carl P
CP
Mitchell
William L
WL
Nicholson
Neville H
NH
Page
Lee W
LW
Patel
Sadhana
S
Roomans
Susan
S
Slingsby
Brian P
BP
Swarbrick
Martin E
ME
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
D000893:Anti-Inflammatory Agents; D007546:Isoquinolines; D011724:Pyridazines; D043885:Receptor, Cannabinoid, CB2