Donepezil Hydrochloride

Химические свойства

Donepezil hydrochloride (E2020) alongside with galantamine and rivastigmine is a piperidine-based drug developed specifically for Alzheimer’s disease (AD) by Eisai Pharmaceuticals (Aricept). Donepezil hydrochloride is commonly referred to in the pharmacological literature as E2020. It has an empirical formula of C24H29NO3HCl and a molecular weight of 415.96. Donepezil hydrochloride is a white crystalline powder and is freely soluble in chloroform, soluble in water and in glacial acetic acid, slightly soluble in ethanol and in acetonitrile, and practically insoluble in ethyl acetate and in n-hexane.

Использование

Donepezil hydrochloride is an inhibitor of acetylcholinesterase with a labelled nootropic. It has been used in dose-response experiment to study its efficacy in ameliorating nicotine withdrawal-induced deficits in contextual conditioning in mice. It has also been intraperitoneally injected into rats to study its ability to improve social behavioral deficits, repetitive behavior and hyperactivity. Labeled Donepezil, intended for use as an internal standard for the quantification of Donepezilby GC- or LC-mass spectrometry.

Подготовка

Donepezil Hydrochloride is being synthesized from alkylidene or arylidene-2-indanone formed by Aldol condensation chemistry as key intermediates (Sugimoto and co-workers)) followed by catalytic reduction affording donepezil hydrochloride with an overall yield of 27%.

Benzyl chloride (1.92 g, 0.0156 mol), potassium carbonate (2.28 g, 0.0165 mol) and PEG-200 (80 mg, 2% by weight) were added to a clear biphasic solution of 2-[(4-piperidyl)methyl]-5,6-dimethoxyindan-1-one 6 (4 g, 0.0138 mol) in 9 : 1 EtOAc–H2O (40 ml). The reaction mixture was heated to 50—55 °C and monitored on TLC. After completion of reaction (14 h), the solid was filtered and the filtrate was washed with water (4 ml). The EtOAc layer was separated, added water (8 ml) and acidified with conc. HCl till a pH 2. EtOAc layer was discarded and the acidic aqueous layer was extracted with CH2Cl2 (2*16 ml). The CH2Cl2 layer was separated, dried over anhydrous Na2SO4, filtered and evaporated under vacuum to yield the crude salt as a residue. The residue was dissolved in methanol (20 ml) followed by the addition of isopropyl ether (40 ml) and stirred for a further 1 h. The precipitated solid was filtered and dried under vacuum to yield pure donepezil hydrochloride.
A New Commercially Viable Synthetic Route for Donepezil Hydrochloride

Определение

ChEBI: Donepezil hydrochloride is a centrally acting reversible acetyl cholinesterase inhibitor. Its main therapeutic use is in the treatment of Alzheimer's disease where it is used to increase cortical acetylcholine.

Общее описание

Pharmaceutical secondary standards for application in quality control, provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to the preparation of in-house working standards.
Donepezil Hydrochloride is known as a selective, reversible inhibitor of acetylcholinesterase enzyme. It exhibits therapeutic effect by raising the acetylcholine concentrations and improving the cholinergic function. It can be used in the treatment of mild to moderate dementia of the Alzheimer′s type.

Фармаколо?гия

Donepezil hydrochloride is a second-generation highly selective acetylcholinesterase inhibitor developed by the Japanese company Eisai Pharmaceutical Company. It was first marketed in the United States in 1997 for the treatment of Alzheimer's disease. Donepezil is the second drug approved by the FDA for the treatment of Alzheimer's disease. It is a highly selective, long-acting, reversible acetylcholinesterase inhibitor with a piperidine group. Compared with tacrine, donepezil hydrochloride is more selective for neuronal acetylcholinease, has better pharmacodynamics, pharmacokinetics and safety indicators, and is well tolerated. It is an alternative drug to tacrine.
Donepezil hydrochloride is a cholinesterase inhibitor. After taking it, patients mainly increase the content of acetylcholine in the synapses that are directly involved in nerve transmission by inhibiting the activity of acetylcholine lipase. Donepezil hydrochloride can Effectively improve patients 'brain function and improve patients' cognitive ability. Currently, donepezil hydrochloride is a commonly used drug in the treatment of mild to moderate senile dementia. Donepezil hydrochloride tablets are suitable for the treatment of memory degeneration of dementia caused by various reasons. Donepezil hydrochloride has the effect of nourishing brain neurons, repairing damaged brain nerves, and can rapidly improve patients' cognitive function and memory.