New synthesis of N1- and N2-substituted pyrazolo[4,3-b]pyridine-5-one derivatives as CB2 receptor ligands

The derivatives of the 7-hydroxy-5-oxopyrazolo[4,3-b]pyridine-6-carboxamide scaffold have been reported recently as potent and selective agonists/inverse agonists of the cannabinoid type-2 receptor (CB2R), but the synthetic way adopted has not yet allowed the structure–activity relationship to be fully explored. Herein, we describe a novel synthetic approach based on the use of a 2-tetrahydropyranyl (THP)-protected precursor that opens the way to obtain either N1- or N2-substituted analogs endowed with agonist or inverse agonist activity, respectively, at the CB2 receptor.