120011-70-3 Usage
Uses
Used in Pharmaceutical Industry:
2,3-Dihydro-5,6-dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-inden-1-one hydrochloride is used as an active pharmaceutical ingredient for the development of drugs targeting the central nervous system. Its complex structure and functional groups allow it to interact with specific receptors or enzymes, potentially leading to therapeutic effects in the treatment of various neurological disorders.
Used in Research and Development:
In the field of medicinal chemistry, this compound serves as a valuable research tool for understanding the structure-activity relationships of various pharmacological agents. It can be used in dose-response experiments and other in vitro and in vivo studies to evaluate its efficacy and safety profile, as well as to optimize its chemical structure for improved performance.
Used in Quality Control and Standardization:
As a pharmaceutical secondary standard, 2,3-Dihydro-5,6-dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-inden-1-one hydrochloride provides a convenient and cost-effective alternative for the preparation of in-house working standards. It can be used to ensure the quality, purity, and consistency of pharmaceutical products, as well as to validate analytical methods and techniques.
Used in Drug Delivery Systems:
Similar to other complex organic compounds, 2,3-Dihydro-5,6-dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-inden-1-one hydrochloride can be incorporated into novel drug delivery systems to improve its bioavailability, targeting, and overall therapeutic efficacy. These systems may include nanoparticles, liposomes, or other advanced formulations designed to enhance the compound's delivery to specific tissues or cells.
Originator
Eisai (Japan)
Preparation
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
Therapeutic Function
Anti-Alzheimer's disease
Biological Activity
donepezil hydrochloride (donepezil hcl) is a novel, potent and selective inhibitor of acetylcholinesterase (ache), an enzyme possibly involved in cognitive dysfunction of patients suffering alzheimer’s disease (ad), with the half maximal inhibition concentration ic50 value of 6.7 nm [1].donepezil hcl is a piperidine-class ache inhibitor containing an n-benzylpiperdine and an indanone moiety, which confers it a longer and more selective action against ache as compared to buche (ic50: 7.4 μm) [1].donepezil hcl has been approved by fda for the treatment of ad, in which it has improved cognitive function of mild to severe moderate ad patients and exhibited excellent tolerability without hepatotoxicity [1].
Biochem/physiol Actions
Donepezil hydrochloride is a piperidine containing an organic compound and a non-competitive inhibitor. It is useful in treating Alzheimer′s disease, in which dementia is a prominent symptom. Donepezil is shown to induce cognitive ability and overall body function. It has a half-life of 70 hours.
Pharmacology
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.
Clinical Use
Treatment of dementia in mild to moderate Alzheimer’s
disease
Side effects
Donepezil was generally well tolerated, although more adverse effects were reported in the 10 mg/day group than assessed as mild to moderate and transient, and were typi-cally diarrhoea，nausea，arthralgia，leg cramps，anorexia and headache. Donepezil (5-10 mg/day) had no effecton V-ADAS-cog but had significant effect on two measuresof executive function: EXIT25 and TMT-B. These subjectswere younger than most VaD patients and most (75%) hadno clinically significant memory dysfunction. The positive effect of donepezil on executive function, however, indicatessome cholinergic deficit in executive dysfunction.
Drug interactions
Potentially hazardous interactions with other drugsNone known
Metabolism
Donepezil hydrochloride is both excreted in the urine
intact and metabolised by the cytochrome P450
system to multiple metabolites, not all of which have
been identified. Following administration of a single
5 mg dose of [14C]-labelled donepezil hydrochloride,
plasma radioactivity, expressed as a percentage of the
administered dose, was present primarily as intact
donepezil hydrochloride (30%), 6-O-desmethyl donepezil
(11% - only metabolite that exhibits activity similar to
donepezil hydrochloride), donepezil-cis-N-oxide (9%),
5-O-desmethyl donepezil (7%) and the glucuronide
conjugate of 5-O-desmethyl donepezil (3%).Approximately 57% of the total administered
radioactivity was recovered from the urine, and 14.5% was
recovered from the faeces, suggesting biotransformation
and urinary excretion as the primary routes of
elimination. There is no evidence to suggest enterohepatic
Check Digit Verification of cas no
The CAS Registry Mumber 120011-70-3 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,2,0,0,1 and 1 respectively; the second part has 2 digits, 7 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 120011-70:
(8*1)+(7*2)+(6*0)+(5*0)+(4*1)+(3*1)+(2*7)+(1*0)=43
43 % 10 = 3
So 120011-70-3 is a valid CAS Registry Number.
InChI:InChI=1/C24H29NO3.ClH/c1-27-22-14-19-13-20(24(26)21(19)15-23(22)28-2)12-17-8-10-25(11-9-17)16-18-6-4-3-5-7-18;/h3-7,14-15,17,20H,8-13,16H2,1-2H3;1H
