title: Discovery of novel cannabinoid receptor ligands by a virtual screening approach: further development of 2,4,6-trisubstituted 1,3,5-triazines as CB2 agonists.
abstract: 3D ligand-based virtual screening was employed to identify novel scaffolds for cannabinoid receptor ligand development. A total of 112 compounds with diverse structures were purchased from commercial vendors. 12 CB1 receptor antagonists/inverse agonists and 10 CB2 receptor agonists were identified in vitro. One of the CB2 agonists, N-cyclopentyl-4-ethoxy-6-(4-methylpiperidin-1-yl)-1,3,5-triazin-2-amine (19, -logEC(50)=7.5, E(max)=255%) was selected for further development. As far as we are aware, the compound's 1,3,5-triazine scaffold represents a new core structure for CB2 agonists. A library of fifty-seven 2,4,6-trisubstituted-1,3,5-triazines was created to clarify the structure-activity relationship study of the analogs.
authors.affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland. sari.yrjola@uef.fi
authors.forename: Sari
authors.initials: S
authors.lastname: Yrjölä
authors.forename: Tuomo
authors.initials: T
authors.lastname: Kalliokoski
authors.forename: Tuomo
authors.initials: T
authors.lastname: Laitinen
authors.forename: Antti
authors.initials: A
authors.lastname: Poso
authors.forename: Teija
authors.initials: T
authors.lastname: Parkkari
authors.forename: Tapio
authors.initials: T
authors.lastname: Nevalainen
mesh_terms: D000465:Algorithms; D008024:Ligands; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000378:metabolism; D054852:Small Molecule Libraries; D013329:Structure-Activity Relationship; D014227:Triazines / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D008024:Ligands; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D054852:Small Molecule Libraries; D014227:Triazines