Alzheimer's disease (AD), the most pervasive form of dementia, remains a universal challenge that must be encountered. It is considered as a serious neurodegenerative disease which can be extensive enough to results in brain shrinkage and death. Although the exact cause of AD is still unclear until now, there are different hypothesis regarding its pathogenesis including beta-amyloid (A?), cholinergic hypothesis, oxidative stress and others. Cholinesterase inhibitors was highlighted to be used against Alzheimer's to inhibit the action of acetylcholinesterase enzyme, which is responsible for breaks down acetylcholine neurotransmitter in the brain tissues. In addition, according to amyloid hypothesis acetylcholinesterase has also non-cholinergic functions that involve stimulation of ?-amyloid accumulation. In this context, different studies have been done on quinazoline hybrids, the promising candidate for AD therapy, for its ability to inhibit acetylcholinesterase (AChE) enzyme and to scavenge excessive amounts of free radicals. As a part xv of an ongoing effort toward identifying potent anti? Alzheimer's agents, we decided to synthesis and study biologically active novel quinazoline derivatives. Compounds 3,4 and 5 has been successfully synthesized in good yields (64%,92.6% and 67%), respectively. An efficient biological evaluation of these compounds for their activity as an acetylcholinesterase inhibitor using Ellman's method was reported. The results showed that compound 3 gave the best IC50 value (13.008 ± 0.43µg/ml) which indicated the most potent one as anticholinesterase inhibitor. All reactions were followed using TLC and characterized their final product using GC-MS, LC-MS, ?H-NMR and ?³C-NMR.