Unique spirocyclopiperazinium salt III: further investigation of monospirocyclopiperazinium (MSPZ) salts as potential analgesics.
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.
Sun
Qi
Q
School of Pharmaceutical Sciences, Peking University, Beijing 100083, PR China.
Yue
Cai-Qin
CQ
Ye
Jia
J
Li
Chang-Ling
CL
Cheng
Tie-Ming
TM
Li
Run-Tao
RT
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
D000700:Analgesics; D010879:Piperazines; D012492:Salts; D013141:Spiro Compounds; C527754:monospirocyclopiperazinium; D004246:Dimethylphenylpiperazinium Iodide