Synthesis and biological activities of some new 1(2H)-phthalazinone derivatives

Alzheimer's disease is a progressive, neurodegenerative and mortal disease that restricts daily activities of individuals, decreases their quality of life in the later stages of the disease, and can be observed as walking disorders and seizures. Epidemiological studies show that the number of patients in the world has doubled every twenty years. Pathological and physicochemical datas based on the experimental studies cannot explain the treatment of this disease. However, some approaches have been developed. The treatment approaches are focusing on cholinesterase inhibition in our current period. But, it is an important problem that the medicines used in clinical practice have serious side effects like excessive cholinergic effect and the hepatotoxicity. Because of significant pharmacological effects of compounds that have phthalazine ring, it's shown that phthalizinone derivatives, one of the most popular members of these group can be investigated. In our study, we have synthesized new 1(2H) -phthalazinone derivative for creating a new anticholinergic agent. For gaining these derivatives, hydrogen and methyl substitutions of the ring were reacted with phthalic and succinic anhydrides and the new molecules are formed. The structures of the compounds were analyzed by spectroscopic methods. The anticholinergic effects of the compounds were measured by comparing donepezil and tacrine that are used in the clinical practice. The highest intermediate level of acetylcholine esterase inhibition was found in the A5 and B2 compounds compared to the other compounds and the highest low level of butyrylcholinesterase inhibition was found in the A3 and B4 compounds.