In order to find more potent analgesics, eight new mono-spirocyclopiperazinium analogues were designed and synthesized by selecting compound 1 as lead compound, which was obtained from our previous works. The structures of target compounds were characterized by ¹H NMR, ¹³C NMR spectra and elemental analysis or HRMS. The synthesized compounds were evaluated for their in vivo analgesic activity by acetic acid induced writhing test. The results indicate that hydroxyl group on the aryl ring is the key pharmacophore and spirocycloammonium salt framework is favorable for the activity. Enlarging the spiro-ring or introducing substituted group is at a disadvantage.

Key words: mono-spirocyclopiperazinium, analgesic activity, synthesis, Mannich reaction, structure-activ- ity relationship