| Alzheimer’s Disease is a neurodegenerative disease that can cause progressive deterioration on memory and cognition. The clinical symptoms of the alzheimer’s disease are characterized by comprehensive dementia performance, memory impairment, agnosia,aphasia, apraxia, executive dysfunction, visual spatial skills damage, personalistic and behavioral changes, and so on. Currently, the pathological mechanism of the alzheimer’s disease has not been well understood, and acetylcholinesterase inhibitor is the main medicine to treat the alzheimer’s disease. These drugs can significantly improve symptoms of AD patients and fewer adverse reactions, however, it is still insufficient to fulfill the requirements of humans. Therefore, to develop a new type of acetylcholinesterase inhibitor is a hot area of current research.In this study, 19 target compounds was synthesized through a sequence of reactions,when 5-aminobenzimidazolone was used as the starting material; and 3-amino-5-phenylpyrazole derivatives was synthesized through a sequence of reactions, when pipiperonal and p-Methoxybenzoic Acid were used as the starting material. All of the target compounds were confirmed by IR,1HNMR and MS spectra.In order to study the biological activity of these compounds, Ellman method was adopted to examine their ACh E inhibitory activity in vitro. The results showed that5 target compounds of 5-aminobenzimidazolone derivatives had a certain inhibitory activity to ACh E. Among them, the bioactivity of 4d was the best, and IC50 of 4d was 7.2 μM, better than that of rivastigmine; 3 target compounds of 3-amino-5-phenyl-pyrazole derivatives had a certain inhibitory activity to ACh E, less than the bioactivity of rivastigmine and huperzine-A.Moreover, the kinetic study of compound 4d was carried out to study the acting mechanism of the compound on acetylcholinesterase, and the Line weaver-Burk plots showed there is a mixed type of competitive inhibition. |
PDF Full Text Request