الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Abstract The thesis is prefaced by a brief literature survey on CNS active agents, especially which deal with epilepsy. Epilepsy is a very common disorder, characterized by seizures, which takes various forms and result from episodic neural discharges. Epilepsy is treated mainly with drugs, though brain surgery may be used for severe cases. Current antiepileptic drugs are effective in controlling seizures in about 70% of patients, but their use is often limited by side effects. 2-Aminothiazole derivatives are widely used structural motifs in medicinal chemistry due to their broad application in drug development. Several reviews and papers about the application of 2-aminothiazoles in the treatment of a diverse range of different diseases like alzheimer’s disease, chronic pain, cancer and Huntington’s disease appeared in the scientific literature over the last few years. In addition to some clinically available AEDs Phenytoin, Ethosuximide and Levetiracetam revealed that many of these compounds included 5-membered cyclic imide moieties in their structures. On these basis a series of 1-(thiazol-2-yl)pyrrolidin-2-ones 117-129 and 2-(thiazol-2-yl)isoindoline-1,3-diones 130-143 were synthesized and evaluated for anticonvulsant activity. The activity was established in three seizure models; pentylenetetrazole (PTZ), picrotoxin and maximum electric shock (MES). selected compounds were selected for neurotoxicity by the rotarod test. The most active compound of the series was 1-(4-(naphthalen-2-yl)thiazol-2-yl)pyrrolidin-2-one (123) showing a PTZ effective dose (ED50) value of 18.4 mg/kg in mice and the median toxic dose (TD50) was 170.2 mg/kg which provided a protection index (PI=TD50/ED50) of 9.2. The mass fragmentation studies were carried on the newly synthesized compounds by two different techniques, namely ion trap and high resolution mass spectrometry to compare the fragmentation patterns in addition to structure confirmation. X-ray crystallographic analyses were also performed on twelve of the synthesized compounds to give detailed stereochemical structural data including the bond lengths and angles and all other details and compare these experimental results with the theoretical results obtained from density function theory (DFT) studies. Results revealed that great similarity in the bond lengths and angles between theoretical and experimental data. Computational studies were also carried out for all the synthesized compounds, including prediction of pharmacokinetic properties ADME and molecular docking studies using several molecular targets; GABA-AT enzyme, NMDA, AMPA, Na+ channel receptors and the human GABAA homology model. Molecular docking results reveal good idea about the possible mechanism of action. The lipophilicity of these compounds expressed as Clog P which computed using software and compared with the experimental data using HPLC.