Optimisation of a novel series of selective CNS penetrant CB2 agonists

A series of benzimidazole CB2 receptor agonists were prepared and their properties investigated. Optimisation of the three benzimidazole substituents led to the identification of compound 23, a potent CB2 full agonist (EC50 2.7 nM) with excellent selectivity over the CB1 receptor (> 3000-fold). Compound 23 demonstrated good CNS penetration in rat. Further optimisation led to the identification of compound 34 with improved selectivity over hERG and excellent CNS penetration in rat. (C) 2011 Elsevier Ltd. All rights reserved.