Chapter 11 Recent Advances in the Discovery of CB2 Selective Agonists

Publisher Summary Novel pain therapeutic alternatives with minimal adverse side effects and abuse potential are highly desired by patients and healthcare professionals. It also discusses the key medicinal chemistry features of this class of compounds, their current clinical trial status and future prospects as therapeutics. The preclinical data that have emerged so far with CB 2 agonists has been promising and suggestive that therapies directed at this target could fulfill this unmet therapeutic need. This chapter describes pharmacological studies using novel CB 2 agonists, which suggest utility for these agents in the treatment of pain and other disorders. Pharmacophore-based de novo virtual screening methods and high-throughput hit-based optimization have been the two main strategies adopted for the discovery of new ligands. A potential role for CB 2 agonists in the treatment of osteoporosis has been proposed based on in vitro suppression of trabecular osteoclasto-genesis because of the inhibition of proliferation of osteoclast precursors and receptor activator of NFkB ligand—RANKL—by the CB 2 agonist. In addition, numerous CB 2 agonists have shown efficacy in multiple animal pain models without apparent CB 1 -associated psychotropic effects.