Discovery of 1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalen-4-carboxamides as potent and selective CB2 receptor agonists

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