السنة | 2019-02-06 |
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التخصص | ماجستير العلوم الصيدلانية |
العنوان | Synthesis of acetylcholinestrase inhibitor as potential drug for the treatment of alzheimer's disease |
اسم المشرف الرئيسي | قيس ابراهيم عبدالله ابوالعسل | Qais Abualassal |
اسم المشرف المشارك | زياد حلمي محمود ابوديه | Zead Abudayeh |
اسم الطالب | فاطمة فتحي عمر الخراز | Fatimah Fathi Omar Alkharaz |
Abstract | Alzheimer's disease (AD) is a neurodegenerative disorder in which the death of brain cells causes memory loss and cognitive decline. The disease starts with mild symptoms and gradually becomes severe. AD is one of the leading causes of mortality worldwide. Several different hallmarks of the disease have been reported such as low levels of acetylcholine, deposits of ?amyloid around neurons, hyperphosphorylated tau protein, oxidative stress, etc. Strategies for prevention of AD through non pharmacological treatments are associated with lifestyle interventions such as exercise, mental challenges, and socialization as well as caloric restriction and a healthy diet. Pharmacotherapy for AD currently depends on using acetylcholinesterase inhibitors (AChEIs) and N-methyl-D-aspartate (NMDA) receptor antagonists. They provide only symptomatic relief and mostly targets cognitive revival. Quinazoline ring scaffold represents a privileged structure that has been utilized to design therapeutic agents for a wide number of diseases. In this research novel quinazoline derivatives 3 and 4 were synthesized starting from 1-N-Methylisatoic anhydride (1) and different analytical methods were utilized for monitoring synthesis and characterization of the target products as TLC, GC-MS and NMR (H1 and C13). Ammonia aqueous solution was reacted with compound 1 to produce compound 2 giving (85.71%) yield, this product has been used to synthesize novel compound 3 through the reaction with cycloheptanone catalyzed by toluene-4-sulfonic acid monohydrate afforded the desired compound (97%) yield. The second novel compound 4 was formed through activation of carbonyl carbon in the amide group of 3 with trimethylsilyl chloride (TMSCl) followed by reduction with lithium aluminium hydride (LiAlH4) giving (73.1%) yield. In this work, the reaction conditions were optimized for the synthesis of 3 and 4 allowing to get them in an excellent yield. |
الأبحاث المستلة |