Synthesis and evaluation of 3-amino-6-aryl-pyridazines as selective CB(2) agonists for the treatment of inflammatory pain

Robert J Gleave; Paul J Beswick; Andrew J Brown; Gerard M P Giblin; Paul Goldsmith; Carl P Haslam; William L Mitchell; Neville H Nicholson; Lee W Page; Sadhana Patel; Susan Roomans; Brian P Slingsby; Martin E Swarbrick

doi:10.1016/j.bmcl.2009.11.117

Synthesis and evaluation of 3-amino-6-aryl-pyridazines as selective CB(2) agonists for the treatment of inflammatory pain

Bioorg Med Chem Lett. 2010 Jan 15;20(2):465-8. doi: 10.1016/j.bmcl.2009.11.117. Epub 2009 Nov 27.

Authors

Robert J Gleave¹, Paul J Beswick, Andrew J Brown, Gerard M P Giblin, Paul Goldsmith, Carl P Haslam, William L Mitchell, Neville H Nicholson, Lee W Page, Sadhana Patel, Susan Roomans, Brian P Slingsby, Martin E Swarbrick

Affiliation

¹ 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. [email protected]

PMID: 20005703
DOI: 10.1016/j.bmcl.2009.11.117

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.

MeSH terms

Animals
Anti-Inflammatory Agents / chemical synthesis*
Anti-Inflammatory Agents / chemistry
Anti-Inflammatory Agents / pharmacokinetics
Isoquinolines / chemical synthesis*
Isoquinolines / chemistry
Isoquinolines / pharmacokinetics
Pain / drug therapy
Pyridazines / chemical synthesis*
Pyridazines / chemistry
Pyridazines / pharmacokinetics
Rats
Receptor, Cannabinoid, CB2 / agonists*
Receptor, Cannabinoid, CB2 / metabolism
Structure-Activity Relationship

Substances

Anti-Inflammatory Agents
Isoquinolines
Pyridazines
Receptor, Cannabinoid, CB2