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Record Information
Version4.0
Creation Date2009-04-06 16:21:37 UTC
Update Date2017-09-27 08:26:56 UTC
HMDB IDHMDB0012242
Secondary Accession Numbers
  • HMDB12242
Metabolite Identification
Common NameKetoconazole
DescriptionKetoconazole is only found in individuals that have used or taken this drug. It is a broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. [PubChem]Ketoconazole interacts with 14-α demethylase, a cytochrome P-450 enzyme necessary for the conversion of lanosterol to ergosterol. This results in inhibition of ergosterol synthesis and increased fungal cellular permeability. Other mechanisms may involve the inhibition of endogenous respiration, interaction with membrane phospholipids, inhibition of yeast transformation to mycelial forms, inhibition of purine uptake, and impairment of triglyceride and/or phospholipid biosynthesis. Ketoconazole can also inhibit the synthesis of thromboxane and sterols such as aldosterone, cortisol, and testosterone.
Structure
Thumb
Synonyms
ValueSource
(2S,4R)-1-Acetyl-4-(4-{[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazineChEBI
1-ACETYL-4-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazineChEBI
(+-)-cis-1-Acetyl-4-(P-((2-(2,4-dichlorophenyl)-2-(imidazol-1- ylmethyl)-1,3-dioxolan-4-yl)methoxy)phenyl)piperazineHMDB
cis-1-Acetyl-4-(4-((2-(2,4-dichlorophenyl)-2-(1H- imidazol-1-ylmethyl)-1,3-dioxolan-4-yl)methoxy)phenyl)-ketoconazolHMDB
FungarestHMDB
FungoralHMDB
KetodermHMDB
KetoisdinHMDB
NizoralHMDB
Orifungal mHMDB
PanfungolHMDB
PiperazineHMDB
Janssen brand OF ketoconazoleMeSH
Ketoconazole janssen brandMeSH
Chemical FormulaC26H28Cl2N4O4
Average Molecular Weight531.431
Monoisotopic Molecular Weight530.148760818
IUPAC Name1-[4-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]ethan-1-one
Traditional Namenizoral
CAS Registry Number65277-42-1
SMILES
CC(=O)N1CCN(CC1)C1=CC=C(OC[C@@H]2CO[C@](CN3C=CN=C3)(O2)C2=CC=C(Cl)C=C2Cl)C=C1
InChI Identifier
InChI=1S/C26H28Cl2N4O4/c1-19(33)31-10-12-32(13-11-31)21-3-5-22(6-4-21)34-15-23-16-35-26(36-23,17-30-9-8-29-18-30)24-7-2-20(27)14-25(24)28/h2-9,14,18,23H,10-13,15-17H2,1H3/t23-,26-/m1/s1
InChI KeyXMAYWYJOQHXEEK-ZEQKJWHPSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as phenylpiperazines. These are compounds containing a phenylpiperazine skeleton, which consists of a piperazine bound to a phenyl group.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganoheterocyclic compounds
Sub ClassDiazinanes
Direct ParentPhenylpiperazines
Alternative Parents
Substituents
  • Phenylpiperazine
  • N-arylpiperazine
  • Aminophenyl ether
  • 1,3-dichlorobenzene
  • Phenol ether
  • Tertiary aliphatic/aromatic amine
  • Phenoxy compound
  • Dialkylarylamine
  • Aniline or substituted anilines
  • Alkyl aryl ether
  • Ketal
  • Halobenzene
  • Chlorobenzene
  • Monocyclic benzene moiety
  • Aryl chloride
  • Aryl halide
  • N-substituted imidazole
  • Benzenoid
  • Meta-dioxolane
  • Heteroaromatic compound
  • Tertiary carboxylic acid amide
  • Imidazole
  • Azole
  • Acetamide
  • Carboxamide group
  • Amino acid or derivatives
  • Tertiary amine
  • Acetal
  • Oxacycle
  • Azacycle
  • Carboxylic acid derivative
  • Ether
  • Organooxygen compound
  • Carbonyl group
  • Organic oxygen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Amine
  • Organonitrogen compound
  • Organochloride
  • Organopnictogen compound
  • Organohalogen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
  • cis-1-acetyl-4-(4-\{[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy\}phenyl)piperazine (CHEBI:47518 )
Ontology
Disposition

Biological Location:

  Subcellular:

  Biofluid and excreta:

Role

Industrial application:

  Pharmaceutical industry:

  Agriculture:

  Food and nutrition:

  Household products:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point146 °CPhysProp
Boiling PointNot AvailableNot Available
Water Solubility0.087 mg/LNot Available
LogP4.35SANGSTER (1993)
Predicted Properties
PropertyValueSource
Water Solubility0.0093 g/LALOGPS
logP4.3ALOGPS
logP4.19ChemAxon
logS-4.8ALOGPS
pKa (Strongest Basic)6.75ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area69.06 ŲChemAxon
Rotatable Bond Count7ChemAxon
Refractivity138.07 m³·mol⁻¹ChemAxon
Polarizability54.67 ųChemAxon
Number of Rings5ChemAxon
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, PositiveNot AvailableView in JSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-001i-3530190000-a2b05a2498270bcd4a7eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-0031490000-58a475e5974da2dfdc18View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0ik9-5395740000-08c010ea5c947e1a62f5View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-014i-9520100000-76672a88c60da8324f81View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00or-2090150000-e4d86d7a4af384399254View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-014i-9240000000-92849351dd004ec26239View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00or-5940000000-e2a0f55e6d356bbc9c0eView in MoNA
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
NameSMPDB/PathwhizKEGG
No entries found
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot Available
Normal
    details
    UrineDetected but not Quantified Not AvailableNot AvailableNormal details
    Abnormal Concentrations
    Not Available
    Predicted Concentrations
    BiofluidValueOriginal ageOriginal sexOriginal conditionComments
    Blood0-2 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
    Blood0-1 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
    Associated Disorders and Diseases
    Disease ReferencesNone
    Associated OMIM IDsNone
    DrugBank IDDB01026
    DrugBank Metabolite IDNot Available
    Phenol Explorer Compound IDNot Available
    Phenol Explorer Metabolite IDNot Available
    FoodDB IDFDB028884
    KNApSAcK IDNot Available
    Chemspider ID43284
    KEGG Compound IDNot Available
    BioCyc IDCPD-4503
    BiGG IDNot Available
    Wikipedia Linkhttp://en.wikipedia.org/wiki/Ketoconazole
    METLIN IDNot Available
    PubChem Compound3823
    PDB IDKLN
    ChEBI ID48339
    References
    Synthesis ReferenceNot Available
    Material Safety Data Sheet (MSDS)Download (PDF)
    General ReferencesNot Available

    Enzymes

    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
    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
    General function:
    Involved in monooxygenase activity
    Specific function:
    Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
    Gene Name:
    CYP2C19
    Uniprot ID:
    P33261
    Molecular weight:
    55944.565
    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
    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.
    Gene Name:
    CYP3A5
    Uniprot ID:
    P20815
    Molecular weight:
    57108.065
    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.
    Gene Name:
    CYP1A1
    Uniprot ID:
    P04798
    Molecular weight:
    58164.815
    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. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
    Gene Name:
    CYP1A2
    Uniprot ID:
    P05177
    Molecular weight:
    58406.915
    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. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti-cancer drug paclitaxel (taxol).
    Gene Name:
    CYP2C8
    Uniprot ID:
    P10632
    Molecular weight:
    55824.275