The Synthesis Of Novel Imidazo-spirocyclic Template And Study On Combinatorial Libraries

The spiro compounds and their derivatives are an important class of drugtemplate compound and have widely applications in the pharmaceuticals. There arearoused extensive concerns in pharmacy and chemistry field for the physiologicalactivities such as antitumor, antidepressant, anxiolytic, anti-thrombotic, antipyreticanalgesic, as well as cure of Alzheimer’s disease and cardiovascular disease.Compared with more research on indole-spirocyclic compounds, very few studieshave been reported on the imidazo-spirocyclic compounds with novel core structureand special physicochemical properties.In this paper, a new imidazo-spirocyclic drug template with novel core structurewas designed, and the corresponding synthetic route was also derived fromretrosynthesis method. After the improvement and optimization of the synthesisprocess, the target drug template was synthesized successfully.According to the Lipinski’s rule of five and WuXi AppTec’s company standard,more than three hundred and forty library compounds were figured out aftermodifying two active substituted groups, following by enumeration and cherry-pick.Based on the parallel synthesis of combinatorial chemistry and different reactionclassification, about three hundred diverse imidazo-spirocyclic library compoundswere obtained. The resulting amount, quality and purity of final product meet theoriginal design requirements and company standard.The successful synthesis and production of imidazo-spirocyclic drug templateand corresponding combinatorial libraries are significant and helpful for furtherstudies and optimization of the lead compound in drug discovery. This drug templateand the corresponding library compounds with the novel, diverse and drug-likeproperties will have a broad market prospects and create considerable economicbenefits for company.