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Record Information
Version4.0
Creation Date2012-09-06 15:16:50 UTC
Update Date2017-09-27 08:27:46 UTC
HMDB IDHMDB0014950
Secondary Accession Numbers
  • HMDB14950
Metabolite Identification
Common NamePhenylbutazone
DescriptionA drug that has anti-inflammatory, antipyretic, and analgesic activities. It is especially effective in the treatment of ankylosing spondylitis. It also is useful in rheumatoid arthritis and Reiter's syndrome (investigational indication). Although phenylbutazone is effective in gouty arthritis, risk/benefit considerations indicate that this drug should not be employed for this disease. (From AMA Drug Evaluations Annual, 1994, p1822)
Structure
Thumb
Synonyms
ValueSource
3,5-dioxo-1,2-Diphenyl-4-N-butylpyrazolidineChEBI
4-BUTYL-1,2-diphenyl-pyrazolidine-3,5-dioneChEBI
4-N-Butyl-1,2-diphenyl-3,5-pyrazolidinedioneChEBI
FenilbutazonaChEBI
PhenbutazoneChEBI
PhenylbutazonChEBI
PhenylbutazonumChEBI
ButacoteMeSH
ButapirazolMeSH
FenilbutazonMeSH
ButadionMeSH
ButadioneMeSH
ButapyrazoleMeSH
ButazolidinMeSH
DiphenylbutazoneMeSH
Chemical FormulaC19H20N2O2
Average Molecular Weight308.3743
Monoisotopic Molecular Weight308.152477894
IUPAC Name4-butyl-1,2-diphenylpyrazolidine-3,5-dione
Traditional Name'esteve'
CAS Registry Number50-33-9
SMILES
CCCCC1C(=O)N(N(C1=O)C1=CC=CC=C1)C1=CC=CC=C1
InChI Identifier
InChI=1S/C19H20N2O2/c1-2-3-14-17-18(22)20(15-10-6-4-7-11-15)21(19(17)23)16-12-8-5-9-13-16/h4-13,17H,2-3,14H2,1H3
InChI KeyVYMDGNCVAMGZFE-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as benzene and substituted derivatives. These are aromatic compounds containing one monocyclic ring system consisting of benzene.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassNot Available
Direct ParentBenzene and substituted derivatives
Alternative Parents
Substituents
  • Monocyclic benzene moiety
  • Pyrazolidinone
  • 1,3-dicarbonyl compound
  • Pyrazolidine
  • Carboxylic acid hydrazide
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Ontology
Disposition

Biological Location:

  Subcellular:

  Biofluid and excreta:

Process

Naturally occurring process:

  Biological process:

    Biochemical pathway:

Role

Industrial application:

  Pharmaceutical industry:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point105 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.14 g/LNot Available
LogP3.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.14 g/LALOGPS
logP2.81ALOGPS
logP4.14ChemAxon
logS-3.3ALOGPS
pKa (Strongest Acidic)5.13ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area40.62 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity88.76 m³·mol⁻¹ChemAxon
Polarizability34.15 ųChemAxon
Number of Rings3ChemAxon
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, Positivesplash10-005c-9450000000-4ff37844132da56b866eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0a4i-0009000000-f8e4cda83d45cc4ca59bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0a4i-0549000000-2907029e48d9c65ae00eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-001i-2910000000-bb1ac78907a0338c7dc6View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-000x-6900000000-4f14a2268cc3ae06d3e5View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0006-9400000000-d5012ae523568dc8e63cView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0006-9100000000-2af914d40adc6817f026View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0006-9000000000-1b11164dde00c44d0ffeView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0006-9000000000-3b304315d58e9e8f6984View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-00kf-9000000000-b6387c41c12a5abb6d4bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0a4i-0009000000-bde0ac035aafd4e337f2View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0006-0092000000-e77e2c9ca9127d3ecff9View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0a4l-0196000000-6d31987fe09f0949a98dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-016r-0190000000-6b839462a4e745d1fc0dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-00vi-0290000000-c78339fd5994808afb08View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0a4i-0109000000-c3cb4b19bc15bf87c709View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-03kl-2921000000-02a08606b3d2e3c8c702View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-01vo-5910000000-1e1a7cd346204d8387aaView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0006-9700000000-b87550cf5df8c862c64aView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-00kf-9500000000-222c301c8bf7fa8c9490View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-1109000000-afb5ea69eff4404428beView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0aou-9276000000-d9698fa12a608213d596View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9110000000-43fc2f7c8c7d34d3c784View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0119000000-bae6357c0badde196104View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-6669000000-1cf1313cd0d66117dd0aView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9300000000-6a338e07dc558445ef7dView in MoNA
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
Pathways
NameSMPDB/PathwhizKEGG
Phenylbutazone Action PathwayPw000678Pw000678 greyscalePw000678 simpleNot Available
Displaying 1 entry
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00812 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00812 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00812
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID4617
KEGG Compound IDC07440
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkPhenylbutazone
METLIN IDNot Available
PubChem Compound4781
PDB IDP1Z
ChEBI ID48574
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Download (PDF)
General ReferencesNot Available

Enzymes

General function:
Involved in peroxidase activity
Specific function:
Mediates the formation of prostaglandins from arachidonate. May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity.
Gene Name:
PTGS2
Uniprot ID:
P35354
Molecular weight:
68995.625
References
  1. Arifah AK, Lees P: Pharmacodynamics and pharmacokinetics of phenylbutazone in calves. J Vet Pharmacol Ther. 2002 Aug;25(4):299-309. [PubMed:12213119 ]
  2. Takada Y, Bhardwaj A, Potdar P, Aggarwal BB: Nonsteroidal anti-inflammatory agents differ in their ability to suppress NF-kappaB activation, inhibition of expression of cyclooxygenase-2 and cyclin D1, and abrogation of tumor cell proliferation. Oncogene. 2004 Dec 9;23(57):9247-58. [PubMed:15489888 ]
  3. Beretta C, Garavaglia G, Cavalli M: COX-1 and COX-2 inhibition in horse blood by phenylbutazone, flunixin, carprofen and meloxicam: an in vitro analysis. Pharmacol Res. 2005 Oct;52(4):302-6. [PubMed:15939622 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
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. Zitova A, Hynes J, Kollar J, Borisov SM, Klimant I, Papkovsky DB: Analysis of activity and inhibition of oxygen-dependent enzymes by optical respirometry on the LightCycler system. Anal Biochem. 2010 Feb 15;397(2):144-51. doi: 10.1016/j.ab.2009.10.029. Epub 2009 Oct 20. [PubMed:19849999 ]
  2. Beretta C, Garavaglia G, Cavalli M: COX-1 and COX-2 inhibition in horse blood by phenylbutazone, flunixin, carprofen and meloxicam: an in vitro analysis. Pharmacol Res. 2005 Oct;52(4):302-6. [PubMed:15939622 ]
  3. Morton AJ, Campbell NB, Gayle JM, Redding WR, Blikslager AT: Preferential and non-selective cyclooxygenase inhibitors reduce inflammation during lipopolysaccharide-induced synovitis. Res Vet Sci. 2005 Apr;78(2):189-92. [PubMed:15563928 ]
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. 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. 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:
Catalyzes the isomerization of prostaglandin H2 to prostacyclin (= prostaglandin I2).
Gene Name:
PTGIS
Uniprot ID:
Q16647
Molecular weight:
57103.385
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Reed GA, Griffin IO, Eling TE: Inactivation of prostaglandin H synthase and prostacyclin synthase by phenylbutazone. Requirement for peroxidative metabolism. Mol Pharmacol. 1985 Jan;27(1):109-14. [PubMed:3917545 ]
  4. Marnett LJ, Siedlik PH, Ochs RC, Pagels WR, Das M, Honn KV, Warnock RH, Tainer BE, Eling TE: Mechanism of the stimulation of prostaglandin H synthase and prostacyclin synthase by the antithrombotic and antimetastatic agent, nafazatrom. Mol Pharmacol. 1984 Sep;26(2):328-35. [PubMed:6434940 ]
  5. Tobin T, Chay S, Kamerling S, Woods WE, Weckman TJ, Blake JW, Lees P: Phenylbutazone in the horse: a review. J Vet Pharmacol Ther. 1986 Mar;9(1):1-25. [PubMed:3517382 ]

Transporters

General function:
Involved in transporter activity
Specific function:
Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds
Gene Name:
SLC22A11
Uniprot ID:
Q9NSA0
Molecular weight:
59970.9
References
  1. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. [PubMed:12130730 ]
General function:
Involved in ion transmembrane transporter activity
Specific function:
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS). Mediates the sodium-independent uptake of p- aminohippurate (PAH), ochratoxin (OTA), acyclovir (ACV), 3'-azido- 3-'deoxythymidine (AZT), cimetidine (CMD), 2,4-dichloro- phenoxyacetate (2,4-D), hippurate (HA), indoleacetate (IA), indoxyl sulfate (IS) and 3-carboxy-4-methyl-5-propyl-2- furanpropionate (CMPF), cidofovir, adefovir, 9-(2- phosphonylmethoxyethyl) guanine (PMEG), 9-(2- phosphonylmethoxyethyl) diaminopurine (PMEDAP) and edaravone sulfate. PAH uptake is inhibited by p- chloromercuribenzenesulphonate (PCMBS), diethyl pyrocarbonate (DEPC), sulindac, diclofenac, carprofen, glutarate and okadaic acid. PAH uptake is inhibited by benzothiazolylcysteine (BTC), S-chlorotrifluoroethylcysteine (CTFC), cysteine S-conjugates S-dichlorovinylcysteine (DCVC), furosemide, steviol, phorbol 12-myristate 13-acetate (PMA), calcium ionophore A23187, benzylpenicillin, furosemide, indomethacin, bumetamide, losartan, probenecid, phenol red, urate, and alpha-ketoglutarate
Gene Name:
SLC22A6
Uniprot ID:
Q4U2R8
Molecular weight:
61815.8
References
  1. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. [PubMed:12130730 ]
  2. Uwai Y, Saito H, Inui K: Interaction between methotrexate and nonsteroidal anti-inflammatory drugs in organic anion transporter. Eur J Pharmacol. 2000 Dec 1;409(1):31-6. [PubMed:11099697 ]
  3. Apiwattanakul N, Sekine T, Chairoungdua A, Kanai Y, Nakajima N, Sophasan S, Endou H: Transport properties of nonsteroidal anti-inflammatory drugs by organic anion transporter 1 expressed in Xenopus laevis oocytes. Mol Pharmacol. 1999 May;55(5):847-54. [PubMed:10220563 ]