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.
Gao
Feng-Li
FL
School of Pharmaceutical Sciences, Peking University, Beijing 100083, PR China.
Wang
Xin
X
Zhang
Hong-Mei
HM
Cheng
Tie-Ming
TM
Li
Run-Tao
RT
D000475:Alkenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D006993:Hypnotics and Sedatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007202:Indicators and Reagents; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010147:Pain Measurement; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000475:Alkenes; D000700:Analgesics; D006993:Hypnotics and Sedatives; D007202:Indicators and Reagents; D010879:Piperazines; D013141:Spiro Compounds