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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:00:38 UTC
Update Date2021-09-14 15:00:47 UTC
HMDB IDHMDB0013968
Secondary Accession Numbers
  • HMDB13968
Metabolite Identification
Common NameHydroxyzileuton
DescriptionHydroxyzileuton is only found in individuals that have used or taken Zileuton. Hydroxyzileuton is a metabolite of Zileuton. Hydroxyzileuton belongs to the family of Benzothiophenes. These are organic compounds containing a benzene fused to a thiepine ring (a five-member ring with six carbon atoms and one sulfur atom).
Structure
Data?1582753158
SynonymsNot Available
Chemical FormulaC11H12N2O3S
Average Molecular Weight252.29
Monoisotopic Molecular Weight252.05686295
IUPAC Name1-hydroxy-1-[1-(6-hydroxy-1-benzothiophen-2-yl)ethyl]urea
Traditional Name1-hydroxy-1-[1-(6-hydroxy-1-benzothiophen-2-yl)ethyl]urea
CAS Registry NumberNot Available
SMILES
CC(N(O)C(N)=O)C1=CC2=CC=C(O)C=C2S1
InChI Identifier
InChI=1S/C11H12N2O3S/c1-6(13(16)11(12)15)9-4-7-2-3-8(14)5-10(7)17-9/h2-6,14,16H,1H3,(H2,12,15)
InChI KeyZQQVPNNYZLDMMO-UHFFFAOYSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as 1-benzothiophenes. These are aromatic heterocyclic compound containing the Benzo[b]thiophene ring system.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzothiophenes
Sub Class1-benzothiophenes
Direct Parent1-benzothiophenes
Alternative Parents
Substituents
  • 1-benzothiophene
  • 2,3,5-trisubstituted thiophene
  • 1-hydroxy-2-unsubstituted benzenoid
  • Benzenoid
  • Thiophene
  • Heteroaromatic compound
  • Carbonic acid derivative
  • Carbonyl group
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Organooxygen compound
  • Organonitrogen compound
  • 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 Solubility0.084 g/LALOGPS
logP1.76ALOGPS
logP1.7ChemAxon
logS-3.5ALOGPS
pKa (Strongest Acidic)8.73ChemAxon
pKa (Strongest Basic)-5.5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area86.79 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity63.94 m³·mol⁻¹ChemAxon
Polarizability25.18 ųChemAxon
Number of Rings2ChemAxon
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]+154.96231661259
DarkChem[M-H]-153.62431661259
DeepCCS[M+H]+150.87230932474
DeepCCS[M-H]-148.51430932474
DeepCCS[M-2H]-181.73530932474
DeepCCS[M+Na]+156.96530932474
AllCCS[M+H]+155.032859911
AllCCS[M+H-H2O]+151.232859911
AllCCS[M+NH4]+158.432859911
AllCCS[M+Na]+159.432859911
AllCCS[M-H]-156.432859911
AllCCS[M+Na-2H]-156.532859911
AllCCS[M+HCOO]-156.632859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
HydroxyzileutonCC(N(O)C(N)=O)C1=CC2=CC=C(O)C=C2S13897.4Standard polar33892256
HydroxyzileutonCC(N(O)C(N)=O)C1=CC2=CC=C(O)C=C2S12093.9Standard non polar33892256
HydroxyzileutonCC(N(O)C(N)=O)C1=CC2=CC=C(O)C=C2S12627.9Semi standard non polar33892256

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
Hydroxyzileuton,1TMS,isomer #1CC(C1=CC2=CC=C(O[Si](C)(C)C)C=C2S1)N(O)C(N)=O2441.2Semi standard non polar33892256
Hydroxyzileuton,1TMS,isomer #2CC(C1=CC2=CC=C(O)C=C2S1)N(O)C(=O)N[Si](C)(C)C2462.4Semi standard non polar33892256
Hydroxyzileuton,2TMS,isomer #1CC(C1=CC2=CC=C(O[Si](C)(C)C)C=C2S1)N(O)C(=O)N[Si](C)(C)C2453.8Semi standard non polar33892256
Hydroxyzileuton,2TMS,isomer #1CC(C1=CC2=CC=C(O[Si](C)(C)C)C=C2S1)N(O)C(=O)N[Si](C)(C)C2519.4Standard non polar33892256
Hydroxyzileuton,2TMS,isomer #1CC(C1=CC2=CC=C(O[Si](C)(C)C)C=C2S1)N(O)C(=O)N[Si](C)(C)C3172.3Standard polar33892256
Hydroxyzileuton,2TMS,isomer #2CC(C1=CC2=CC=C(O)C=C2S1)N(O)C(=O)N([Si](C)(C)C)[Si](C)(C)C2537.8Semi standard non polar33892256
Hydroxyzileuton,2TMS,isomer #2CC(C1=CC2=CC=C(O)C=C2S1)N(O)C(=O)N([Si](C)(C)C)[Si](C)(C)C2624.4Standard non polar33892256
Hydroxyzileuton,2TMS,isomer #2CC(C1=CC2=CC=C(O)C=C2S1)N(O)C(=O)N([Si](C)(C)C)[Si](C)(C)C3257.2Standard polar33892256
Hydroxyzileuton,3TMS,isomer #1CC(C1=CC2=CC=C(O[Si](C)(C)C)C=C2S1)N(O)C(=O)N([Si](C)(C)C)[Si](C)(C)C2474.4Semi standard non polar33892256
Hydroxyzileuton,3TMS,isomer #1CC(C1=CC2=CC=C(O[Si](C)(C)C)C=C2S1)N(O)C(=O)N([Si](C)(C)C)[Si](C)(C)C2589.1Standard non polar33892256
Hydroxyzileuton,3TMS,isomer #1CC(C1=CC2=CC=C(O[Si](C)(C)C)C=C2S1)N(O)C(=O)N([Si](C)(C)C)[Si](C)(C)C2908.9Standard polar33892256
Hydroxyzileuton,1TBDMS,isomer #1CC(C1=CC2=CC=C(O[Si](C)(C)C(C)(C)C)C=C2S1)N(O)C(N)=O2719.8Semi standard non polar33892256
Hydroxyzileuton,1TBDMS,isomer #2CC(C1=CC2=CC=C(O)C=C2S1)N(O)C(=O)N[Si](C)(C)C(C)(C)C2731.3Semi standard non polar33892256
Hydroxyzileuton,2TBDMS,isomer #1CC(C1=CC2=CC=C(O[Si](C)(C)C(C)(C)C)C=C2S1)N(O)C(=O)N[Si](C)(C)C(C)(C)C2945.4Semi standard non polar33892256
Hydroxyzileuton,2TBDMS,isomer #1CC(C1=CC2=CC=C(O[Si](C)(C)C(C)(C)C)C=C2S1)N(O)C(=O)N[Si](C)(C)C(C)(C)C2902.9Standard non polar33892256
Hydroxyzileuton,2TBDMS,isomer #1CC(C1=CC2=CC=C(O[Si](C)(C)C(C)(C)C)C=C2S1)N(O)C(=O)N[Si](C)(C)C(C)(C)C3282.2Standard polar33892256
Hydroxyzileuton,2TBDMS,isomer #2CC(C1=CC2=CC=C(O)C=C2S1)N(O)C(=O)N([Si](C)(C)C(C)(C)C)[Si](C)(C)C(C)(C)C2969.3Semi standard non polar33892256
Hydroxyzileuton,2TBDMS,isomer #2CC(C1=CC2=CC=C(O)C=C2S1)N(O)C(=O)N([Si](C)(C)C(C)(C)C)[Si](C)(C)C(C)(C)C2966.9Standard non polar33892256
Hydroxyzileuton,2TBDMS,isomer #2CC(C1=CC2=CC=C(O)C=C2S1)N(O)C(=O)N([Si](C)(C)C(C)(C)C)[Si](C)(C)C(C)(C)C3250.5Standard polar33892256
Hydroxyzileuton,3TBDMS,isomer #1CC(C1=CC2=CC=C(O[Si](C)(C)C(C)(C)C)C=C2S1)N(O)C(=O)N([Si](C)(C)C(C)(C)C)[Si](C)(C)C(C)(C)C3191.0Semi standard non polar33892256
Hydroxyzileuton,3TBDMS,isomer #1CC(C1=CC2=CC=C(O[Si](C)(C)C(C)(C)C)C=C2S1)N(O)C(=O)N([Si](C)(C)C(C)(C)C)[Si](C)(C)C(C)(C)C3127.0Standard non polar33892256
Hydroxyzileuton,3TBDMS,isomer #1CC(C1=CC2=CC=C(O[Si](C)(C)C(C)(C)C)C=C2S1)N(O)C(=O)N([Si](C)(C)C(C)(C)C)[Si](C)(C)C(C)(C)C3138.6Standard polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Hydroxyzileuton GC-MS (Non-derivatized) - 70eV, Positivesplash10-004l-3900000000-0bdea288f9e16d003d8c2017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Hydroxyzileuton GC-MS (1 TMS) - 70eV, Positivesplash10-05r0-1900000000-5198e17adbd0699e04b92017-10-06Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Hydroxyzileuton 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 - Hydroxyzileuton 10V, Positive-QTOFsplash10-0w29-0190000000-8e78cea746aff6d0e5602016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Hydroxyzileuton 20V, Positive-QTOFsplash10-0ik9-2490000000-54ad52e711135e2b735b2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Hydroxyzileuton 40V, Positive-QTOFsplash10-004i-2900000000-bb9be06d9b6741ae5d312016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Hydroxyzileuton 10V, Negative-QTOFsplash10-0k96-7290000000-16fd8ffd8d7795dbe5512016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Hydroxyzileuton 20V, Negative-QTOFsplash10-052f-9480000000-84fe315ad03945067ad82016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Hydroxyzileuton 40V, Negative-QTOFsplash10-0006-9500000000-0dfedd364e419f7a0dad2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Hydroxyzileuton 10V, Negative-QTOFsplash10-0006-9200000000-c711bc896a0675b56a412021-09-22Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Hydroxyzileuton 20V, Negative-QTOFsplash10-0007-3900000000-32b7f66d095b512c67752021-09-22Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Hydroxyzileuton 40V, Negative-QTOFsplash10-0002-2900000000-451158baa83584ee77ab2021-09-22Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Hydroxyzileuton 10V, Positive-QTOFsplash10-004i-0900000000-f71b86df29926e80d9fe2021-09-23Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Hydroxyzileuton 20V, Positive-QTOFsplash10-004i-0910000000-60edf4cb5f08a28ab7962021-09-23Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Hydroxyzileuton 40V, Positive-QTOFsplash10-06vl-1900000000-ac99ae34207e651728eb2021-09-23Wishart 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 ID35032780
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNot Available
METLIN IDNot Available
PubChem Compound131750722
PDB IDNot Available
ChEBI ID145222
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 transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols.
Gene Name:
UGT1A9
Uniprot ID:
O60656
Molecular weight:
59940.495
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 metal ion binding
Specific function:
Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes.
Gene Name:
ALOX5
Uniprot ID:
P09917
Molecular weight:
77982.595
References
  1. Wenzel SE: Leukotriene receptor antagonists and related compounds. Can Respir J. 1999 Mar-Apr;6(2):189-93. [PubMed:10322101 ]
  2. Hardy DB, Pereria LE, Yang K: Prostaglandins and leukotriene B4 are potent inhibitors of 11beta-hydroxysteroid dehydrogenase type 2 activity in human choriocarcinoma JEG-3 cells. Biol Reprod. 1999 Jul;61(1):40-5. [PubMed:10377029 ]
  3. Yamashita M, Kushihara M, Hirasawa N, Takasaki W, Takahagi H, Takayanagi M, Ohuchi K: Inhibition by troglitazone of the antigen-induced production of leukotrienes in immunoglobulin E-sensitized RBL-2H3 cells. Br J Pharmacol. 2000 Jan;129(2):367-73. [PubMed:10694244 ]
  4. Qian C, Hwang SB, Libertine-Garahan L, Eckman JB, Cai X, Scannell RT, Yeh CG: Anti-inflammatory activities of LDP-392, a dual PAF receptor antagonist and 5-lipoxygenase inhibitor. Pharmacol Res. 2001 Sep;44(3):213-20. [PubMed:11529688 ]
  5. Coffey MJ, Phare SM, Peters-Golden M: Peroxynitrite-induced nitrotyrosination of proteins is blocked by direct 5-lipoxygenase inhibitor zileuton. J Pharmacol Exp Ther. 2001 Oct;299(1):198-203. [PubMed:11561080 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  7. Zouboulis CC: Zileuton, a new efficient and safe systemic anti-acne drug. Dermatoendocrinol. 2009 May;1(3):188-92. [PubMed:20436887 ]
  8. Zouboulis CC, Seltmann H, Alestas T: Zileuton prevents the activation of the leukotriene pathway and reduces sebaceous lipogenesis. Exp Dermatol. 2010 Feb;19(2):148-50. doi: 10.1111/j.1600-0625.2009.00929.x. Epub 2009 Jul 23. [PubMed:19645854 ]
  9. Berger W, De Chandt MT, Cairns CB: Zileuton: clinical implications of 5-Lipoxygenase inhibition in severe airway disease. Int J Clin Pract. 2007 Apr;61(4):663-76. [PubMed:17394438 ]
  10. Guidot DM, Repine MJ, Westcott JY, Repine JE: Intrinsic 5-lipoxygenase activity is required for neutrophil responsivity. Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):8156-9. [PubMed:8058773 ]
  11. Wenzel SE, Kamada AK: Zileuton: the first 5-lipoxygenase inhibitor for the treatment of asthma. Ann Pharmacother. 1996 Jul-Aug;30(7-8):858-64. [PubMed:8826571 ]
General function:
Involved in peroxidase activity
Specific function:
May play an important role in regulating or promoting cell proliferation in some normal and neoplastically transformed cells.
Gene Name:
PTGS1
Uniprot ID:
P23219
Molecular weight:
68685.82
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:
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. Machinist JM, Mayer MD, Shet MS, Ferrero JL, Rodrigues AD: Identification of the human liver cytochrome P450 enzymes involved in the metabolism of zileuton (ABT-077) and its N-dehydroxylated metabolite, Abbott-66193. Drug Metab Dispos. 1995 Oct;23(10):1163-74. [PubMed:8654206 ]
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:
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
References
  1. Wang B, Zhou SF: Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218. [PubMed:19754423 ]
  2. 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 ]
  3. Machinist JM, Mayer MD, Shet MS, Ferrero JL, Rodrigues AD: Identification of the human liver cytochrome P450 enzymes involved in the metabolism of zileuton (ABT-077) and its N-dehydroxylated metabolite, Abbott-66193. Drug Metab Dispos. 1995 Oct;23(10):1163-74. [PubMed:8654206 ]