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The antiepileptic drug topiramate synthesis and process research

Author: TianBin
Tutor: LiWenHong
School: Northwestern University
Course: Pharmaceutical Engineering
Keywords: Topiramate antiepileptic drug D-fructose synthesis optimized technology
CLC: TQ463.53
Type: Master's thesis
Year: 2010
Downloads: 65
Quote: 0
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Abstract


Epilepsy is the most common of the nervous system disease, the patient about 50 millions in the global, and the treatment is still dominated by drugs at present. Before the appearance of the new antiepileptic drugs, the therapy method is mainly depends on the traditional one. But the limitations of the pharmacokinetics, the possibility of the teratogenicity, and the bad effect on cognitive functioning, which limit their applications. The invention of antiepileptic drugs and applications bring the epilepsy sufferers with hope and more choices.As a new type of antiepileptic drug, Topiramate is the sulphur generation product of the natural state, D-fructos. It has the high bioavailability, long acting time and many obvious advantages. In addition. it has the multiple role of the mechanism, good effect on many types of epileptic in clinical treatment. Its tolerance and security are also good, and belongs to powerful and broad spectrum antiepileptic drug.On the basis of synthetic methods reported in literatures, the systematic study on the synthesis process was carried out, and the conditions of the key unit reaction in the synthesis were improved. This method avoids the using of highly toxic and corrosive materials, have the advantage of mild react conditions, easy operation, and security. All of that is appropriate for magnifying and industrial production. The structure of the Topiramate and its key intermediate products were characterized by element analysis, infrared analysis and melt point determinate.Main contents and The innovations:(1) The diacetonefructose was obtained with D-fructose and acetone, and the concentrated sulphuric acid was used as catalyzer. The possible effect factors to the yield of the product were also studied and the optimal inventory, reactor temperature and time were confirmed.(2) The chlorosulfate, a important intermediate product, prepared with sulfuric chloride and diacetonefructose. The dichloroethane was replaced by dichloromethane in this paper, that is, the use of toxic solvent was greatly reduced. Besides, the improvement of the feeding method avoids the appear of the vigorous reaction which can lead to by-product and low yield.(3) With ammonia water to replace the reaction of ammonia can make operator simple and safe, and decrease the equipment costs, the solid product can be obtained by extract and condense the solvent, which is benefit to industrialized production.

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CLC: > Industrial Technology > Chemical Industry > Pharmaceutical chemical industry > Production of organic compounds in drug > Heterocyclic compounds drugs > Five section heterocyclic
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