Rapid assessment of a novel series of selective CB(2) agonists using parallel synthesis protocols: A Lipophilic Efficiency (LipE) analysis.
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.
Ryckmans
Thomas
T
Pfizer Discovery Chemistry, Ramsgate Road, Sandwich CT139NJ Kent, United Kingdom. thomas.ryckmans@pfizer.com
Edwards
Martin P
MP
Horne
Val A
VA
Correia
Ana Monica
AM
Owen
Dafydd R
DR
Thompson
Lisa R
LR
Tran
Isabelle
I
Tutt
Michelle F
MF
Young
Tim
T
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
D008024:Ligands; D043885:Receptor, Cannabinoid, CB2; D013449:Sulfonamides; D009584:Nitrogen