Unique spirocyclopiperazinium salt. Part 2: synthesis and structure–activity relationship of dispirocyclopiperazinium salts as analgesics

Abstract

Three series of spirocyclopiperazinium derivatives 5a– d, 6a– f and 17a– d were synthesized and evaluated for their in vivo analgesic activities. Compounds 5a, 17a and 17b exhibited excellent analgesic activity. Two important structure–activity relationships were observed from this study: (1) the quaternary ammonium functionality is a critical pharmacophore for analgesic activity; (2) it is important to adjust the lipophilic property of compounds to improve analgesic activity.