1 research outputs found
CB2-Selective Cannabinoid Receptor Ligands: Synthesis, Pharmacological Evaluation, and Molecular Modeling Investigation of 1,8-Naphthyridin-2(1<i>H</i>)‑one-3-carboxamides
We
have recently identified 1,8-naphthyridin-2Â(1<i>H</i>)-one-3-carboxamide
as a new scaffold very suitable for the development
of new CB2 receptor potent and selective ligands. In this paper we
describe a number of additional derivatives in which the same central
scaffold has been variously functionalized in position 1 or 6. All
new compounds showed high selectivity and affinity in the nanomolar
range for the CB2 receptor. Furthermore, we found that their functional
activity is controlled by the presence of the substituents at position
C-6 of the naphthyridine scaffold. In fact, the introduction of substituents
in this position determined a functionality switch from agonist to
antagonists/inverse agonists. Finally, docking studies showed that
the difference between the pharmacology of these ligands may be in
the ability/inability to block the Toggle Switch W6.48(258) (χ1 <i>g+</i> → <i>trans</i>) transition