Synthesis and structure–analgesic activity relationships of a novel series of monospirocyclopiperazinium salts (MSPZ)

✍ Scribed by Song-Wen Lin; Qi Sun; Ze-Mei Ge; Xin Wang; Jia Ye; Run-Tao Li

• Publisher: Elsevier Science
• Year: 2011
• Tongue: English
• Weight: 293 KB
• Volume: 21
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/j.bmcl.2010.12.052

✦ Synopsis

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.