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Design and synthesis of a potential lead compound quinazoline-lipoic acid derivative for the treatment of Alzheimers disease
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Fatimah Mueen Alhudaby
Alzheimer’s disease (AD) is one of most common neurodegenerative disorder and irreversible form of dementia in elderly people and the available treatment for this disease is only symptomatic and doesn’t delay the disease progression. Alzheimer’s disease is multi-factorial disease involved several pathological hypothesis mainly cholinergic and oxidative stress hypothesis. Quinazolie moiety had been reported in many previous studies that had inhibition activity against AChE the main enzyme in cholinergic hypothesis and also had free radical scavenging activity. In this work we designed and synthesized a novel hybrid compound of quinazoline-lipoic acid (compound 5) which supposed to have dual activity to delay the progression of AD. Compound 4 synthesized starting from N-methyl isatoic anhydride in 3 steps then coupled with lipoic acid using thionyl chloride, the reactions monitored with TLC and the final ptoduct characterized by GC-MS, H-NMR and C-NMR.