Design,Synthesis And Anti-Osteoporosis Activity Of Tricyclic Diterpene Heterocyclic Analogues

With the accelerating pace of population aging,the number of people suffering from osteoporosis will be increasing and bring heavy burden to the society and family.The existing clinical drugs posses side effects and can not treat osteoporosis ideally.Accordingly,the development of new anti-osteoporosis drugs has become an urgent need.In recent years,many new structure of tricyclic diterpenoids are constantly being discovered.As they have a wide range of biological activity,scientists pay more attention to them.In our previous study,we synthesized a series of tricyclic diterpene analogues and tested for anti-osteoporosis.We found that heterocyclic compound 22 showed high activity.Based on the lead compound 22,we designed and synthesized a series of tricyclic diterpene heterocyclic analogues and tested for anti-osteoporosis activity.Results showed that compound 39 had the best activity with inhibition of 72.3%at 0.1 ?M,and it almost completely inhibited the differentiation of osteoclast at concentration of 2.0?M.Preliminary biological toxicity assay confirmed that compound 39 had a high index of safety in cell level.Relevent evaluation in vivo and biological mechanism study are in progressing.This thesis provides a new idea for the research and development of new drugs for osteoporosis.