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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:00:36 UTC
Update Date2021-09-16 15:29:20 UTC
HMDB IDHMDB0013958
Secondary Accession Numbers
  • HMDB13958
Metabolite Identification
Common Name5-O-Desmethyldonepezil
Description5-O-Desmethyldonepezil 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. 5-O-Desmethyldonepezil is a very strong basic compound (based on its pKa).
Structure
Data?1582753157
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
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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPiperidines
Sub ClassBenzylpiperidines
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
Physiological effectNot Available
Disposition
ProcessNot Available
RoleNot Available
Physical Properties
StateNot Available
Experimental Molecular Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Experimental Chromatographic PropertiesNot Available
Predicted Molecular 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
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DarkChem[M+H]+187.22531661259
DarkChem[M-H]-184.61231661259
DeepCCS[M+H]+195.39430932474
DeepCCS[M-H]-193.03630932474
DeepCCS[M-2H]-227.24130932474
DeepCCS[M+Na]+202.51130932474
AllCCS[M+H]+191.032859911
AllCCS[M+H-H2O]+188.332859911
AllCCS[M+NH4]+193.532859911
AllCCS[M+Na]+194.232859911
AllCCS[M-H]-192.332859911
AllCCS[M+Na-2H]-192.532859911
AllCCS[M+HCOO]-192.932859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
5-O-DesmethyldonepezilCOC1=C(O)C=C2CC(CC3CCN(CC4=CC=CC=C4)CC3)C(=O)C2=C13981.5Standard polar33892256
5-O-DesmethyldonepezilCOC1=C(O)C=C2CC(CC3CCN(CC4=CC=CC=C4)CC3)C(=O)C2=C13140.3Standard non polar33892256
5-O-DesmethyldonepezilCOC1=C(O)C=C2CC(CC3CCN(CC4=CC=CC=C4)CC3)C(=O)C2=C13262.0Semi standard non polar33892256

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
5-O-Desmethyldonepezil,1TMS,isomer #1COC1=CC2=C(C=C1O[Si](C)(C)C)CC(CC1CCN(CC3=CC=CC=C3)CC1)C2=O3143.3Semi standard non polar33892256
5-O-Desmethyldonepezil,1TBDMS,isomer #1COC1=CC2=C(C=C1O[Si](C)(C)C(C)(C)C)CC(CC1CCN(CC3=CC=CC=C3)CC1)C2=O3366.2Semi standard non polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - 5-O-Desmethyldonepezil GC-MS (Non-derivatized) - 70eV, Positivesplash10-0076-7962000000-cd9808b75874a019166b2017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - 5-O-Desmethyldonepezil GC-MS (1 TMS) - 70eV, Positivesplash10-00dl-9425400000-49a8ba9cbb54b0f1ecf62017-10-06Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - 5-O-Desmethyldonepezil GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - 5-O-Desmethyldonepezil GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 5-O-Desmethyldonepezil 10V, Negative-QTOFsplash10-03di-0019000000-acb0a258339ab79c2c4d2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 5-O-Desmethyldonepezil 20V, Negative-QTOFsplash10-03di-0239000000-74fddf8c4efdfa5d49b62016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 5-O-Desmethyldonepezil 40V, Negative-QTOFsplash10-056r-6792000000-9eb8cbce74a27d2636c02016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 5-O-Desmethyldonepezil 10V, Negative-QTOFsplash10-03di-0009000000-ffffb190b205b7f90e412021-09-23Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 5-O-Desmethyldonepezil 20V, Negative-QTOFsplash10-03di-1009000000-868002d9b616da08db7f2021-09-23Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 5-O-Desmethyldonepezil 40V, Negative-QTOFsplash10-03di-1149000000-7e629881ae7e0217d4502021-09-23Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 5-O-Desmethyldonepezil 10V, Positive-QTOFsplash10-014l-3209000000-50a5e17dc83b7a7e3b3c2016-08-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 5-O-Desmethyldonepezil 20V, Positive-QTOFsplash10-0006-9422000000-d773292e758d958f40e82016-08-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 5-O-Desmethyldonepezil 40V, Positive-QTOFsplash10-0006-9000000000-b2ca1c86f200fd45024b2016-08-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 5-O-Desmethyldonepezil 10V, Positive-QTOFsplash10-014i-0009000000-a1d0f5f0342c7143f6652021-09-22Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 5-O-Desmethyldonepezil 20V, Positive-QTOFsplash10-014i-3109000000-44569b0ed40c21fef6bd2021-09-22Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 5-O-Desmethyldonepezil 40V, Positive-QTOFsplash10-0006-9143000000-d23d5abcad6fd43b06d72021-09-22Wishart LabView Spectrum
Biological Properties
Cellular Locations
  • Extracellular
Biospecimen Locations
  • Blood
  • Urine
Tissue Locations
  • Kidney
  • Liver
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FooDB 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
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
Good Scents 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 ]