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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:00:36 UTC
Update Date2017-12-07 02:44:18 UTC
HMDB IDHMDB0013958
Secondary Accession Numbers
  • HMDB13958
Metabolite Identification
Common Name5-O-Desmethyldonepezil
Description5-O-Desmethyldonepezil is only found in individuals that have used or taken Donepezil. 5-O-Desmethyldonepezil is a metabolite of Donepezil. 5-o-desmethyldonepezil belongs to the family of Indanones. These are compounds containing an indane ring bearing a ketone group.
Structure
Thumb
SynonymsNot Available
Chemical FormulaC23H27NO3
Average Molecular Weight365.4654
Monoisotopic Molecular Weight365.199093735
IUPAC Name2-[(1-benzylpiperidin-4-yl)methyl]-5-hydroxy-6-methoxy-2,3-dihydro-1H-inden-1-one
Traditional Name2-[(1-benzylpiperidin-4-yl)methyl]-5-hydroxy-6-methoxy-2,3-dihydroinden-1-one
CAS Registry NumberNot Available
SMILES
COC1=C(O)C=C2CC(CC3CCN(CC4=CC=CC=C4)CC3)C(=O)C2=C1
InChI Identifier
InChI=1S/C23H27NO3/c1-27-22-14-20-18(13-21(22)25)12-19(23(20)26)11-16-7-9-24(10-8-16)15-17-5-3-2-4-6-17/h2-6,13-14,16,19,25H,7-12,15H2,1H3
InChI KeyDSMISVLYMKJMLP-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as n-benzylpiperidines. These are heterocyclic Compounds containing a piperidine ring conjugated to a benzyl group through one nitrogen ring atom.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganoheterocyclic compounds
Sub ClassPiperidines
Direct ParentN-benzylpiperidines
Alternative Parents
Substituents
  • N-benzylpiperidine
  • Indanone
  • Indane
  • Anisole
  • Benzylamine
  • Phenylmethylamine
  • Aryl ketone
  • Aryl alkyl ketone
  • Alkyl aryl ether
  • 1-hydroxy-2-unsubstituted benzenoid
  • Aralkylamine
  • Monocyclic benzene moiety
  • Benzenoid
  • Tertiary aliphatic amine
  • Tertiary amine
  • Ketone
  • Ether
  • Azacycle
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Amine
  • Organic nitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Ontology
Disposition

Biological Location:

  Subcellular:

  Biofluid and excreta:

  Organ and components:

  Cell and elements:

Source:

Role

Biological role:

Industrial application:

  Pharmaceutical industry:

Physical Properties
StateNot Available
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.021 g/LALOGPS
logP4.14ALOGPS
logP3.18ChemAxon
logS-4.2ALOGPS
pKa (Strongest Acidic)8.06ChemAxon
pKa (Strongest Basic)8.76ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area49.77 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity107.63 m³·mol⁻¹ChemAxon
Polarizability42.29 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0076-7962000000-cd9808b75874a019166bView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-00dl-9425400000-49a8ba9cbb54b0f1ecf6View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014l-3209000000-50a5e17dc83b7a7e3b3cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0006-9422000000-d773292e758d958f40e8View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9000000000-b2ca1c86f200fd45024bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-0019000000-acb0a258339ab79c2c4dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03di-0239000000-74fddf8c4efdfa5d49b6View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-056r-6792000000-9eb8cbce74a27d2636c0View in MoNA
Biological Properties
Cellular Locations
  • Extracellular
Biofluid Locations
  • Blood
  • Urine
Tissue Location
  • Kidney
  • Liver
PathwaysNot Available
NameSMPDB/PathwhizKEGG
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDDBMET00127
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID9678036
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNot Available
METLIN IDNot Available
PubChem Compound11503234
PDB IDNot Available
ChEBI IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot Available

Enzymes

General function:
Involved in carboxylesterase activity
Specific function:
Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
Gene Name:
ACHE
Uniprot ID:
P22303
Molecular weight:
67795.525
References
  1. Davis KL: Alzheimer's disease: seeking new ways to preserve brain function. Interview by Alice V. Luddington. Geriatrics. 1999 Feb;54(2):42-7; quiz 48. [PubMed:10024872 ]
  2. Kryger G, Silman I, Sussman JL: Structure of acetylcholinesterase complexed with E2020 (Aricept): implications for the design of new anti-Alzheimer drugs. Structure. 1999 Mar 15;7(3):297-307. [PubMed:10368299 ]
  3. Shepherd G, Klein-Schwartz W, Edwards R: Donepezil overdose: a tenfold dosing error. Ann Pharmacother. 1999 Jul-Aug;33(7-8):812-5. [PubMed:10466911 ]
  4. Kosasa T, Kuriya Y, Matsui K, Yamanishi Y: Effect of donepezil hydrochloride (E2020) on basal concentration of extracellular acetylcholine in the hippocampus of rats. Eur J Pharmacol. 1999 Sep 10;380(2-3):101-7. [PubMed:10513568 ]
  5. Jann MW: Rivastigmine, a new-generation cholinesterase inhibitor for the treatment of Alzheimer's disease. Pharmacotherapy. 2000 Jan;20(1):1-12. [PubMed:10641971 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  7. Sugimoto H: Donepezil hydrochloride: a treatment drug for Alzheimer's disease. Chem Rec. 2001;1(1):63-73. [PubMed:11893059 ]
  8. Ki YS, Park EY, Lee HW, Oh MS, Cho YW, Kwon YK, Moon JH, Lee KT: Donepezil, a potent acetylcholinesterase inhibitor, induces caspase-dependent apoptosis in human promyelocytic leukemia HL-60 cells. Biol Pharm Bull. 2010;33(6):1054-9. [PubMed:20522977 ]
  9. Repantis D, Laisney O, Heuser I: Acetylcholinesterase inhibitors and memantine for neuroenhancement in healthy individuals: a systematic review. Pharmacol Res. 2010 Jun;61(6):473-81. doi: 10.1016/j.phrs.2010.02.009. Epub 2010 Mar 1. [PubMed:20193764 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014 ]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular weight:
55627.365
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014 ]
General function:
Involved in monooxygenase activity
Specific function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014 ]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production
Gene Name:
HTR2A
Uniprot ID:
P28223
Molecular weight:
52602.6
References
  1. Hayslett RL, Tizabi Y: Effects of donepezil, nicotine and haloperidol on the central serotonergic system in mice: implications for Tourette's syndrome. Pharmacol Biochem Behav. 2005 Aug;81(4):879-86. [PubMed:16045972 ]
  2. Hayslett RL, Tizabi Y: Effects of donepezil on DOI-induced head twitch response in mice: implications for Tourette syndrome. Pharmacol Biochem Behav. 2003 Dec;76(3-4):409-15. [PubMed:14643839 ]