Studies On The Synthesis And Analgesic And Anti-inflammatory Quantitative Structure-activity Relationships (QSAR) Of Sinomenine's Derivatives

Objective: Study the analgesic and anti-inflammatory QSAR of sinomenine's derivatives.Methods: On the basis of sinomenine as lead-compound, seven derivatives were synthesized via acylation, alkylation on its 4- phenol hydroxyl groups; though the analgesic model of writhing response induced by acetic acid in mouse and anti-inflammatory model of the rat's hind paw edema induced by carrageenan, the analgesic and anti-inflammatory effects of these derivatives were evaluated, their ED₅₀ were also calculated; Hansch's model was adopted to deal with experimental result mathematically and got the equation of QSAR..Results: The basic structure of these compounds are proved by IR, Ms and 1H-NMR; the established QSAR equation was logl/c=-2.032+0.184 Ï€ (Analgesic, R²=0.779, F=21.136) andlogl/c=-2.598+0.198 Ï€ (Anti-inflammatory, R²=0.951, F=116.731)Conclusions: The higher analgesic and anti-inflammatory activities were showed when the phenol groups of sinomenine replaced by the lipophilic groups.