Discovery of 1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalen-4-carboxam i des as potent and selective CB sub(2) receptor agonists

The design and synthesis of novel 1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalen-4-carboxam i de CB sub(2) selective ligands for the potential treatment of pain is described. Compound (R,R)-25 has good balance between CB sub(2) agonist potency and selectivity over CB sub(1), and possesses overall favorable pharmaceutical properties. It also demonstrated robust in vivo efficacy mediated via CB sub(2) activation in the rodent models of inflammatory and osteoarthritis pain after oral administration.