engleski

Application of NMR for monitoring the synthetic route and characterization of bisacrbamates

Because of its conformational and metabolic stability, the ability to pass through the cell membrane and creating favorable interactions between both molecules and drugs, the carbamate group has become a desirable part of many drugs in different applications field. Today, four carbamate-based drugs are approved for the treatment of neurodegenerative diseases, whose primary action is inhibition of cholinesterases, the enzymes responsible for the hydrolysis of acetylcholine, a neurotransmitter in the central nervous system: rivastigmine for the treatment of Alzheimer`s (AD), physostigmine for Parkinson`s disease, and neostigmine and pyridostigmine for myasthenia gravis. With the aim of developing new multi-target drugs for the treatment of AD, targeting cholinesterases and beta-secretase activities new biscarbamates were designed and synthesized. These new compounds have carbamate groups in the meta position because, according to our previous study, the meta-position of carbamate groups on the benzene ring assures an easier entrance of biscarbamates and its orientation into the active site of cholinesetrases. Additionally, propargylamine in the amine part of the molecules is used to ensure the inhibition of beta- secretases. All of the biscarbamates were obtained from a five- step synthetic route starting from 3, 5- dihydroxyacetophenone. During the synthesis, we used NMR 1H spectroscopy as a fast and versatile technique to monitor the course of reaction and confirm the obtainment of the desired intermediates, which we used in the next step of the synthesis. The structure of final products of our five-step synthetic route was verified with 1H and 13C NMR spectroscopy

synthesis ; biscarbamates ; cholinesterases ; NMR

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