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

摘要

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, -log EC50 = 7.5, Emax = 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. ? 2012 Elsevier B.V. All rights reserved.