title: Synthesis and structure-analgesic activity relationships of a novel series of monospirocyclopiperazinium salts (MSPZ).
abstract: A series of monospirocyclopiperazinium salts were designed and synthesized to search for a peripherally-acting analgesic drug with low side effects. Extensive SAR studies revealed that a suitable NR(2)R(3) was critical for the analgesic activity, which might be beneficial to expose the cationic nitrogen to bind to the receptor, and possibly interact with the receptor via π-π interaction. Introduction of substituting group on the N(4)-phenyl ring could improve the activity, and the best position was the 4-position. Compound 14n showed more potent analgesic activity (63%, 20 μM/kg, sc) and holds promise for development as a mechanically new analgesic drug.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, PR China.
authors.forename: Song-Wen
authors.initials: SW
authors.lastname: Lin
authors.forename: Qi
authors.initials: Q
authors.lastname: Sun
authors.forename: Ze-Mei
authors.initials: ZM
authors.lastname: Ge
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Jia
authors.initials: J
authors.lastname: Ye
authors.forename: Run-Tao
authors.initials: RT
authors.lastname: Li
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D051379:Mice; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D012492:Salts / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D010879:Piperazines; D012492:Salts