The Synthesis Of Nitric Oxide Donor Conjugated Ketone Derivatives Of Topiramate Where Inflammatory And Analgesic Activity

The synthesis and structure-activity relationship(SAR) of NO-coupled 3H-1,2-dihydro-1-pyrrolizinones are reported in this paper.3H-1,2-dihydro-1-pyrrolizinone was discovered to be a lead compound with highly antiinflammatory and analgesic effective in the structure transformation of senecionine, which is the effctive ingredient of folk medicine-gynura root. Fourteen new NO-coupled compounds of 3H-1,2-dihydro-1-pyrrolizinone have been designed and synthesized based on the advances of research of the nonsteroidal anti-inflammatory drugs(NSAIDs). Their chemical structures have been confirmed by IR, ~1HNMR, and MS.Pharmacological studies show that most of the compounds have antiinflammatory and analgesic activity in different extent, in which LM-6,LM-9,LM-10 have significant antiinflammatory activity. Some SAR of these compounds was summarized.