Unique spirocyclopiperazinium salt I: synthesis and structure–Activity relationship of spirocyclopiperazinium salts as analgesics

Based on the structure of compound 3, two series of spirocyclopiperazinium derivatives 7a–n and 10a–h were synthesized and evaluated for their in vivo analgesic and sedative activities. Compounds 7f and 10c were discovered to exhibit excellent analgesic activity. Structure–activity relationships revealed that anion of the quaternary salt affected the analgesic and sedative activity significantly; the allyl group is a most effective group among the compounds 7a–n; the electron-released substitute on the aromatic ring is favorable to increase the analgesic activity.