ChemFOnt: Showing chemical card for Donepezil (CFc000002381)

Record Information

Version

1.0

Creation Date

2022-08-28 10:25:12 UTC

Update Date

2022-09-13 18:47:15 UTC

Chemfont ID

CFc000002381

Molecule Identification

Common Name

Donepezil

Definition

Donepezil, marketed under the trade name Aricept (Eisai), 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. It has an oral bioavailability of 100% and easily crosses the blood-brain barrier. Because it has a half life of about 70 hours, it can be taken once a day. Initial dose is 5 mg per day, which can be increased to 10 mg per day after an adjustment period of at least 4 weeks. Donepezil 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. It is well absorbed in the gut with an oral bioavailability of 100% and easily crosses the blood-brain barrier. Because it has a half life of about 70 hours, it can be taken once a day. Currently, there is no definitive proof that use of donepezil or other similar agents alters the course or progression of Alzheimer's disease. However, 6-12 month controlled studies have shown modest benefits in cognition and/or behavior. Pilot studies have reported that donepezil therapy may potentially have effects on markers of disease progression, such as hippocampal volume. Therefore, many neurologists, psychiatrists, and primary care physicians use donepezil in patients with Alzheimer's disease. In 2005, the UK National Institute for Clinical Excellence (NICE) withdrew its recommendation for use of the drug for mild-to-moderate AD, on the basis that there is no significant improvement in functional outcome; Currently, there is no definitive proof that use of donepezil or other similar agents alters the course or progression of Alzheimer's disease. However, 6-12 month controlled studies have shown modest benefits in cognition and/or behavior. Pilot studies have reported that donepezil therapy may potentially have effects on markers of disease progression, such as hippocampal volume. Therefore, many neurologists, psychiatrists, and primary care physicians use donepezil in patients with Alzheimer's disease. In 2005, the UK National Institute for Clinical Excellence (NICE) withdrew its recommendation for use of the drug for mild-to-moderate AD, on the basis that there is no significant improvement in functional outcome; of quality of life or of behavioral symptoms. However, NICE revised its guidelines to suggest that donepezil be used in moderate stage patients for whom the evidence is strongest. While the drug is currently indicated for mild to moderate Alzheimer's, there is also evidence from 2 trials that it may be effective for moderate to severe disease. An example of this is a Karolinska Institute paper published in The Lancet in early 2006, which states that donepezil improves cognitive function even in patients with severe Alzheimer's disease symptoms. of quality of life or of behavioral symptoms. However, NICE revised its guidelines to suggest that donepezil be used in moderate stage patients for whom the evidence is strongest. While the drug is currently indicated for mild to moderate Alzheimer's, there is also evidence from 2 trials that it may be effective for moderate to severe disease. An example of this is a Karolinska Institute paper published in The Lancet in early 2006, which states that donepezil improves cognitive function even in patients with severe Alzheimer's disease symptoms.

Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
Donepezilo	ChEBI
Donepezilum	ChEBI
Donaz	Kegg
Aricept	HMDB, MeSH
Aricept odt	HMDB
Donepezil hydrochloride	HMDB, MeSH
1-Benzyl-4-((5,6-dimethoxy-1-indanon)-2-yl)methylpiperidine hydrochloride	MeSH, HMDB
Donepezilium oxalate trihydrate	MeSH, HMDB
Eranz	MeSH, HMDB

Chemical Formula

C₂₄H₂₉NO₃

Average Molecular Weight

379.492

Monoisotopic Molecular Weight

379.214743799

IUPAC Name

2-[(1-benzylpiperidin-4-yl)methyl]-5,6-dimethoxy-2,3-dihydro-1H-inden-1-one

Traditional Name

donepezil

CAS Registry Number

120014-06-4

SMILES

COC1=C(OC)C=C2C(=O)C(CC3CCN(CC4=CC=CC=C4)CC3)CC2=C1

InChI Identifier

InChI=1S/C24H29NO3/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

InChI Key

ADEBPBSSDYVVLD-UHFFFAOYSA-N

Chemical Taxonomy

Description

Belongs to the class of organic compounds known as n-benzylpiperidines. These are heterocyclic Compounds containing a piperidine ring conjugated to a benzyl group through one nitrogen ring atom.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Piperidines

Sub Class

Benzylpiperidines

Direct Parent

N-benzylpiperidines

Alternative Parents

Substituents

N-benzylpiperidine
Indanone
Indane
Aryl alkyl ketone
Aryl ketone
Phenylmethylamine
Benzylamine
Anisole
Aralkylamine
Alkyl aryl ether
Benzenoid
Monocyclic benzene moiety
Tertiary aliphatic amine
Tertiary amine
Ketone
Azacycle
Ether
Organic nitrogen compound
Organic oxygen compound
Organopnictogen compound
Organic oxide
Hydrocarbon derivative
Organooxygen compound
Organonitrogen compound
Amine
Aromatic heteropolycyclic compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

piperidines (CHEBI:53289 )
cyclic ketone (CHEBI:53289 )

Functional Ontology

Physiological effect

Health effect

Observation

Nervous system disorder

Coma (HMDB: HMDB0005041)

Central nervous system disorder

Psychiatric disorder

Neurotic, stress-related, or somatoform disorder

Anxiety (HMDB: HMDB0005041)

Mood disorder

Major depressive disorder (HMDB: HMDB0005041)

Circulatory system disorder

Vascular disorder

Hypertension (HMDB: HMDB0005041)
Hypotension (HMDB: HMDB0005041)

Blood and lymphatic system disorder

Hypoglycemia (HMDB: HMDB0005041)

Disposition

Biological location

Cellular substructure

Membrane (HMDB: HMDB0005041)
Cell membrane (HMDB: HMDB0005041)

Organ

Brain (HMDB: HMDB0005041)

Route of exposure

Enteral

Ingestion (HMDB: HMDB0005041)

Source

Exogenous

Exogenous (HMDB: HMDB0005041)

Process

Not Available

Role

Industrial application

Nootropic agent (HMDB: HMDB0005041)

Pharmaceutical industry

Pharmaceutical (HMDB: HMDB0005041)

Biological role

Modulator

Inhibitor

EC 3.1.1.8 (cholinesterase) inhibitor (HMDB: HMDB0005041)
EC 3.1.1.7 (acetylcholinesterase) inhibitor (HMDB: HMDB0005041)

Physical Properties

Predicted Properties

Property	Value	Source
Water Solubility	0.0045 g/L	ALOGPS
logP	4.14	ALOGPS
logP	4.21	ChemAxon
logS	-4.9	ALOGPS
pKa (Strongest Acidic)	17.02	ChemAxon
pKa (Strongest Basic)	8.62	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	4	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	38.77 Å²	ChemAxon
Rotatable Bond Count	6	ChemAxon
Refractivity	112.11 m³·mol⁻¹	ChemAxon
Polarizability	44.34 Å³	ChemAxon
Number of Rings	4	ChemAxon
Bioavailability	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

External Links

HMDB ID

Not Available

DrugBank ID

Not Available

Phenol Explorer Compound ID

Not Available

FooDB ID

Not Available

KNApSAcK ID

Not Available

Chemspider ID

3040

KEGG Compound ID

Not Available

BioCyc ID

Not Available

BiGG ID

Not Available

Wikipedia Link

Donepezil

METLIN ID

Not Available

PubChem Compound

Not Available

PDB ID

Not Available

ChEBI ID

53289

Food Biomarker Ontology

Not Available

References

Synthesis Reference

Sugimoto, Hachiro; Tsuchiya, Yutaka; Higurashi, Kunizou; Karibe, Norio; Iimura, Yuoichi; Sasaki, Atsushi; Yamanashi, Yoshiharu; Ogura, Hiroo; Araki, Shin; et al. Preparation of 1-benzyl-4-(substituted alkyl)piperidines and analogs as acetylcholinesterase inhibitors. Eur. Pat. Appl. (1988), 103 pp. CODEN: EPXXDW EP 296560 A2 19881228 CAN 110:173102 AN 1989:173102

Showing chemical card for Donepezil (CFc000002381)

MOL for CFc000002381 (Donepezil)

3D MOL for CFc000002381 (Donepezil)

3D SDF for CFc000002381 (Donepezil)

3D-SDF for CFc000002381 (Donepezil)

PDB for CFc000002381 (Donepezil)

3D PDB for CFc000002381 (Donepezil)

SMILES for CFc000002381 (Donepezil)

INCHI for CFc000002381 (Donepezil)

Structure for CFc000002381 (Donepezil)

3D Structure for CFc000002381 (Donepezil)