Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) are two cholinesterases that are known to hydrolyze acetylcholine, a neurotransmitter essential for regulating neurological activity. In Alzheimer’s disease (AD), low levels of acetylcholine are directly correlated with a decrease in cognitive function and neurodegenerative disorders. Currently, drugs such as Donepezil are used to treat AD by inhibiting AChE, thereby increasing acetylcholine levels. We have been interested in exploring the use of organophosphorus compounds as cholinesterase inhibitors. Our recent studies with the dialkyl phenyl phosphates (DAPP) showed selective inhibition of BuChE without affecting AChE activity. In this work, procedures used to synthesize DAPPs were applied to generate a series of dialkyl 2-chlorophenyl phosphates as potential BuChE inhibitors. A refinement in the synthetic methods for these compounds was also employed to generate bivalent organophosphorus dimers.
|Commitee:||Acey, Roger A., Marinez, Eric R.|
|School:||California State University, Long Beach|
|School Location:||United States -- California|
|Source:||MAI 52/03M(E), Masters Abstracts International|
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