Unique spirocyclopiperazinium salt. Part 2: synthesis and structure-activity relationship of dispirocyclopiperazinium salts as analgesics.
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.
Wang
Xin
X
School of Pharmaceutical Sciences, Peking University, Beijing 100083, PR China.
Gao
Feng-Li
FL
Piao
Hong-Bin
HB
Cheng
Tie-Ming
TM
Li
Run-Tao
RT
D000700:Analgesics / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D057927:Hydrophobic and Hydrophilic Interactions; D006993:Hypnotics and Sedatives / Q000138:chemical synthesis / Q000494:pharmacology; D020714:Maximum Tolerated Dose; D051379:Mice; D010879:Piperazines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D012492:Salts; D013141:Spiro Compounds; D013329:Structure-Activity Relationship
D000700:Analgesics; D006993:Hypnotics and Sedatives; D010879:Piperazines; D012492:Salts; D013141:Spiro Compounds