Donepezil Hydrochloride
DONEPEZIL HCL · ARICEPT · Donepezi · Donepezil-d7 Hydrochloride · bnag · E-2020 · AKOS 226-31 · DOPEZIL HCL
식별자 및 물리적 특성
| CAS No. | 120011-70-3 |
|---|---|
| 분자식 | C24H30ClNO3 |
| 평균 분자량 | 416 g/mol |
| 단동위원소 질량 | 415.1914215 g/mol |
| SMILES | COc1cc2c(cc1OC)C(=O)C(CC1CCN(Cc3ccccc3)CC1)C2.Cl |
| InChIKey | XWAIAVWHZJNZQQ-UHFFFAOYSA-N |
| PubChem CID | 5741 |
| ChEMBL | CHEMBL1678 |
| EC No. | 620-543-2 |
| DTXSID | DTXSID0046698 |
화학 및 물리적 성질
| 극성 표면적 | 38.8 |
|---|---|
| 수소 결합 공여자 수 | 1 |
| 수소 결합 수용자 수 | 4 |
| 회전 가능 결합 수 | 6 |
| 무거운 원자 수 | 29 |
| 형식 전하 | 0 |
| 복잡도 | 510 |
| Collision Cross Section | 196.6 Ų [M+H]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards] |
| 녹는점 | 220-222°C |
| 저장 조건 | room temp |
| 용해도 | 물에 용해됨 |
| 용해도 | insoluble in EtOHinsoluble in DMSO≥10.4 mg/mL in H2O |
| 물리적 상태 | 가루 |
| 색상 | 흰색에서 황백색까지 |
| Merck | 14,3419 |
| 안정성 | 흡습성 |
| InChI | InChI=1S/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,8-13,16H2,1-2H31H |
| InChIKey | XWAIAVWHZJNZQQ-UHFFFAOYSA-N |
| SMILES | C1(=O)C2=C(C=C(OC)C(OC)=C2)CC1CC1CCN(CC2=CC=CC=C2)CC1.[H]Cl |
화학적 성질
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.
안전 및 규제
| GHS 분류 | DangerH300 (17.9%): Fatal if swallowed [Danger Acute toxicity, oral]H301 (76.2%): Toxic if swallowed [Danger Acute toxicity, oral]H319 (79.8%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]P264, P264+P265, P270, P280, P301+P316, P305+P351+P338, P321, P330, P337+P317, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 84 reports by companies from 15 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website. |
|---|---|
| Hazard Classes and Categories | Acute Tox. 2 (17.9%)Acute Tox. 3 (76.2%)Eye Irrit. 2 (79.8%) |
| Treatment | If the compound has been ingested, rapid gastric lavage should be performed using 5% sodium bicarbonate. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of isotonic saline or water. In serious cases, atropine and/or pralidoxime should be administered. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of '-oximes' has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally. |
| 건강 영향 | Acute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergi |
| 노출 경로 | Donepezil is well absorbed with a relative oral bioavailability of 100% and reaches peak plasma concentrations in 3 to 4 hours. |
| 독성 요약 | Donepezil is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen. |
| Signs and Symptoms | Symptoms of overdose include severe nausea, vomiting, salivation, sweating, bradycardia, hypotension, respiratory depression, collapse and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. |
| Carcinogen Classification | No indication of carcinogenicity to humans (not listed by IARC). |
| Drug Induced Liver Injury | Drug Induced Liver Injury Rank (DILIrank 2.0)Donepezil hydrochloridevLess-DILI-concern3Adverse reactionsDOI:10.1016/j.drudis.2016.02.015 |
| 수질 위해 등급(WGK) | 1 |
| RTECS 번호 | NK8927885 |
| 운송 번호(UN) | UN 2811 |
| 관세 코드 | 2933.39.9200 |
| 위험 문구(R) | 36/37/38 |
| 위험 표시 | Xi |
| 안전 문구(S) | 26-36 |
| 포장분류 | II |
| 위험 등급 | 6.1Acute Tox. 2 OralEye Irrit. 2 |
| 저장 분류 | 6.1A - Combustible acute toxic Cat. 1 and 2very toxic hazardous materials |
용도
용도
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.
일반 설명
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.
제조 및 합성 방법
제조 방법
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