ABSTRACT
A series of alpha-amidosulfones were found to be potent and selective agonists of CB(2). The discovery, synthesis, and structure-activity relationships of this series of agonists are reported. In addition, the pharmacokinetic properties of the most promising compounds are profiled.
Subject(s)
Receptor, Cannabinoid, CB2/agonists , Sulfones/chemistry , Amides/chemistry , Amides/pharmacology , Animals , Humans , Microsomes, Liver , Pharmacokinetics , Rats , Structure-Activity Relationship , Sulfones/pharmacologyABSTRACT
Structural modifications to the central portion of the N-arylamide oxadiazole scaffold led to the identification of N-arylpiperidine oxadiazoles as conformationally constrained analogs that offered improved stability and comparable potency and selectivity. The simple, modular scaffold allowed for the use of expeditious and divergent synthetic routes, which provided two-directional SAR in parallel. Several potent and selective agonists from this novel ligand class are described.
