Design, Synthesis And Biological Evaluation Of The Analogs Of Noscapine

Noscapine, a tetrahydroisoquinoline alkaloid isolated from opium, was widely used as a classical peripheral antitussive agent. In recent years, it has aroused extensive and systematic study because of its high anti-tumor activity, low toxicity and unique acting mechanism.Here particularly introduced the relationship between the microtubule and tumor, the mechanism of anti-tumor drugs interfering the microtubule and the research development of noscapine and its analogue’s anti-tumor activity. Based on the previous researching results in our group,37 compounds were designed and synthesized via further simplification and modification of the lead——Noscapine.24 of them have not yet been reported in literatures. The chemical structures of the target compounds were confirmed by 1H NMR and ESI-MS, some of which were further confirmed by NOESY for the determination of their relative configuration.Primary pharmacological tests showed that some of the target compounds had some inhibitory activity, amongst them LQ-11 showed the best inhibitory activity. Based upon the results of the pharmacological test, the structure and activity relationships (SAR) were briefly summarized in this thesis.