Design, Synthesize Of Pyridazine's Double Derivatives And Preliminary Research Of Pharmacodynamics For Alzheimer's Disease

Alzheimer's disease (AD) is the most common form of dementia. This incurable, degenerative, and terminal disease was first described by German psychiatrist Alois Alzheimer in 1906 and was named after him. Alzheimer's disease is a brain disorder in which nerve cells in the brain die, making it difficult for the brain's signals to be transmitted properly. A person with Alzheimer's disease has problems with memory, judgment, and thinking, which makes it hard for the person to work or take part in day-to-day life. Research indicates that the disease is associated with plaques and tangles in the brain. The risk of developing Alzheimer's disease increases with age. According to the Alzheimer's AssociationWe design and synthesize five new pyridazine'double derivates, and inspect the preliminary research of pharmacodynamics for AD.In addition, using the natural active product as the leading compound, to find high-effect and low-poison have been the effective method for finding new drug. Osthole is a kind of novel coumarin separated from the natural plant Common Cnidium Fruit, which has the effects of improving brain function, enhancing memory and an-ti AD activity. It exert its function mainly through the mechanisms of inhibiting the cholinesterase's activity, raising the level of acetylcholine in brain. But its activity is low. we firstly use the microwave-assisted method to optimize the extractive conditions of osthole from Common Cnidium Fruit t through orthogonal design method. we do the structural modification of osthole: firstly establish the method of synthesis of 7-hydroxy osthole, and firstly establish the method of microwave-assisted synthesis of pyridazine's osthole double derivates.My research article mainly includes the following four parts:First, synthesis of pyridazine'double derivates.Based on the bridge of pyridazine, design five new pyridazine'double derivates, choose and establish the convenient synthesis method for the target products.Second, microwave extraction method research on osthole.The microwave-assisted process for extraction of osthole have never been reported. In this article, we firstly use the microwave-assisted method to optimize the extractive conditions of osthole from Common Cnidium Fruit t through orthogonal design method. Compared with normal reflux method, microwave-assisted extraction of osthole is more useful.Thirdly, structural modification of osthole.To enhance the Center- selectivity of osthole, we do the structural modification of osthole: firstly establish the method of synthesis of 7-hydroxy osthole, and firstly use the method of microwave-assisted synthesis of pyridazine's osthole double derivates. Fourthly, preliminary research of pharmacodynamics for AD.Investigate effects of DEOP-2 on Aβ_1-42'aggregation and PC12 Cell apoptosis induced by Aβ_1-42 in vitro. Use Th-T mark the fibriform Aβ, and method of immunofluorescence to observe the effect of s on Aβ_1-42'aggregation; and PC12 cells were incubated with Aβ_1-42 and DEOP -2. Cell viability was detected by MTT. Results: DEOP -2 can resist the adverse effects of Aβ_1-42 on increasing apoptotic rates, and it has the protective function towards nerve cells.