Synthesis and biological activities study of novel phthalimides and phenylpyrazolo[1,5-a]pyrimidines

Abstract

Phosphodiesterase II (PDE2) is mainly distributed in brain and heart cells, and it is a potential therapeutic target for the treatment of central nervous system (CNS) diseases such as Alzheimer’s disease. Based on the structure of the existing PDE2 inhibitor BAY60-7550, a series of novel phthalimides and phenylpyrazolo[1,5- a]pyrimidines have been designed and prepared. Furthermore, after evaluating their inhibitory activity toward PDE2, compound 7-oxo- N-phenethyl-5-phenyl-4,7-dihydropyrazolo[1,5- a]pyrimidine-3-carboxamide is found to have the optimum inhibitory potential (IC50: 1.82 ± 0.29 μM). Discovery Studio software used to simulate the structure–activity relationship between this compound and the PDE2 protein crystal 4HTX to illustrate the binding modes, which provides favorable guidance for the further development of effective PDE2 inhibitors.