title: Unique spirocyclopiperazinium salt III: further investigation of monospirocyclopiperazinium (MSPZ) salts as potential analgesics.
abstract: Two novel classes of monospirocyclopiperazinium salts were designed, synthesized, and evaluated for their in vivo analgesic activities. Some interesting structure-activity relationships are revealed: (1) Spirocyclopiperazinium moiety is favorable to improve the analgesic activity; (2) The size and conformation of spirocyclopiperazinium moiety significantly affects the analgesic activity; (3) Phenylethyl group of 3d is a crucial pharmacophore. Among the compounds synthesized, 3d exhibited the most potent activity with low toxicity. Further antinociceptive mechanism studies of 3d showed that these compounds will be a new kind of analgesics.
authors: School of Pharmaceutical Sciences, Peking University, Beijing 100083, PR China.
authors: Qi
authors: Q
authors: Sun
authors: Cai-Qin
authors: CQ
authors: Yue
authors: Jia
authors: J
authors: Ye
authors: Chang-Ling
authors: CL
authors: Li
authors: Tie-Ming
authors: TM
authors: Cheng
authors: Run-Tao
authors: RT
authors: Li
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D004246:Dimethylphenylpiperazinium Iodide / Q000737:chemistry / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D051379:Mice; D015394:Molecular Structure; D010147:Pain Measurement; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D012492:Salts; D013141:Spiro Compounds / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D010879:Piperazines; D012492:Salts; D013141:Spiro Compounds; C527754:monospirocyclopiperazinium; D004246:Dimethylphenylpiperazinium Iodide