الفهرس 
THEORETICALOnly 14 pages are availabe for public view
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Abstract
Considering the several theories and suggestions enlightening the relevance and design of novel compounds that are used for the treatment of Alzheimer’s disease, assisted by a comprehensive literature survey on the importance of m1-subtype selective muscarinic agonists as a unique therapy for that disease, specially those containing thiadiazole moieties in their structures, the synthesis of novel series of compounds that carry the main structural features contributing to m1-selective agonistic activity was promoted, aiming to attain a curative effect towards Alzheimer’s disease. In the present investigation, new series of 3-alkoxy-4-substituted amino-1,2,5-thiadiazole-1-oxides, 3-(4-fluorobenzylamino)-4-(un)substituted amino-1,2,5-thiadiazole-1-oxides, 3-(2-adamantyl- amino)-4-(un)substituted amino-1,2,5-thiadiazole-1-oxides and 4-(4-fluorobenzyl)-8-substituted-4,8-dihydro bis [1,2,5]-thiadiazolo[3,4-b:3’ ,4’-e]pyrazine-2,6-dioxide systems were prepared. In order to obtain the target compounds, different chemical pathways were adopted and found to be successful. In the present study, twenty novel compounds that are not mentioned in the available literature were synthesized. The formation and purity of the newly synthesized compounds were checked by TLC, and their structures were elucidated through elemental microanalyses, IR, 1H-NMR and mass spectroscopy. Seventeen of the newly synthesized compounds were subjected to preliminary in vitro screening for muscarinic agonistic activity, using isolated rabbit intestine, acetylcholine as reference drug and atropine as non selective muscarinic antagonist. Six compounds showed improved agonistic activity towards muscarinic receptors, two exhibited moderate activity, while nine compounds showed no activity. Compounds that proved to be muscarinic agonists need further investigation to be tested for selectivity towards m1-receptors using the selective m1-selective antagonist, (pirenzepine).