title: Rapid assessment of a novel series of selective CB(2) agonists using parallel synthesis protocols: A Lipophilic Efficiency (LipE) analysis.
abstract: A series of libraries were designed using the 1-(cyclopropylmethyl)-2-alkyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-5-ium templates 2a-b, and Sulfonamide derivatives 11a-n proved to be potent agonists of the CB(2) receptor. Analysis of the Lipophilic Efficiency (LipE) of potent compounds provided new insight for the design of potent, metabolically stable CB2 agonists.
authors.affiliation: Pfizer Discovery Chemistry, Ramsgate Road, Sandwich CT139NJ Kent, United Kingdom. thomas.ryckmans@pfizer.com
authors.forename: Thomas
authors.initials: T
authors.lastname: Ryckmans
authors.forename: Martin P
authors.initials: MP
authors.lastname: Edwards
authors.forename: Val A
authors.initials: VA
authors.lastname: Horne
authors.forename: Ana Monica
authors.initials: AM
authors.lastname: Correia
authors.forename: Dafydd R
authors.initials: DR
authors.lastname: Owen
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Thompson
authors.forename: Isabelle
authors.initials: I
authors.lastname: Tran
authors.forename: Michelle F
authors.initials: MF
authors.lastname: Tutt
authors.forename: Tim
authors.initials: T
authors.lastname: Young
mesh_terms: D000818:Animals; D001665:Binding Sites; D002626:Chemistry, Pharmaceutical / Q000379:methods; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D020128:Inhibitory Concentration 50; D008024:Ligands; D008862:Microsomes, Liver / Q000187:drug effects; D008956:Models, Chemical; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry; D051381:Rats; D043885:Receptor, Cannabinoid, CB2 / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry
chemical_list: D008024:Ligands; D043885:Receptor, Cannabinoid, CB2; D013449:Sulfonamides; D009584:Nitrogen