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Identification
NamePhenylbutazone
Accession NumberDB00812  (APRD00409, DB08343)
TypeSmall Molecule
GroupsApproved
Description

A 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
SynonymLanguageCode
3,5-Dioxo-1,2-diphenyl-4-n-butylpyrazolidineNot AvailableNot Available
4-BUTYL-1,2-diphenyl-pyrazolidine-3,5-dioneNot AvailableNot Available
4-n-Butyl-1,2-diphenyl-3,5-pyrazolidinedioneNot AvailableNot Available
FenilbutazonaNot AvailableNot Available
PhenbutazoneNot AvailableNot Available
PhenylbutazonNot AvailableNot Available
PhenylbutazoneNot AvailableNot Available
PhenylbutazonumNot AvailableNot Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
AzolidNot Available
Brand mixtures
Brand NameIngredients
Alka Phenyl TabAluminum Hydroxide + Magnesium Trisilicate + Phenylbutazone
Alka Phenylbutazone TabAluminum Hydroxide + Magnesium Trisilicate + Phenylbutazone
Phenylone Plus TabAluminum Hydroxide + Magnesium Trisilicate + Phenylbutazone
SaltsNot Available
Categories
CAS number50-33-9
WeightAverage: 308.3743
Monoisotopic: 308.152477894
Chemical FormulaC19H20N2O2
InChI KeyVYMDGNCVAMGZFE-UHFFFAOYSA-N
InChI
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
IUPAC Name
4-butyl-1,2-diphenylpyrazolidine-3,5-dione
SMILES
CCCCC1C(=O)N(N(C1=O)C1=CC=CC=C1)C1=CC=CC=C1
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
  • 1,3-dicarbonyl compound
  • Pyrazolidinone
  • Monocyclic benzene moiety
  • Pyrazolidine
  • Carboxylic acid hydrazide
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of backache and ankylosing spondylitis
PharmacodynamicsPhenylbutazone is a synthetic, pyrazolone derivative. It is a nonhormonal anti-inflammatory, antipyretic compound useful in the management of inflammatory conditions. The apparent analgesic effect is probably related mainly to the compound's anti-inflammatory properties and arise from its ability to reduce production of prostaglandin H and prostacyclin. Prostaglandins act on a variety of cells such as vascular smooth muscle cells causing constriction or dilation, on platelets causing aggregation or disaggregation and on spinal neurons causing pain. Prostacylcin causes vascular constriction platelet disaggregation
Mechanism of actionPhenylbutazone binds to and inactivates prostaglandin H synthase and prostacyclin synthase through peroxide (H2O2) mediated deactivation. The reduced production of prostaglandin leads to reduced inflammation of the surrounding tissues.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityOral, LD50 = 238 mg/kg (mouse); Oral, LD50 = 781 mg/kg (rabbit); Oral, LD50 = 245 mg/kg (rat); Oral, LD50 = 375 mg/kg (rat)
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Phenylbutazone Action PathwayDrug actionSMP00701
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9931
Caco-2 permeable+0.6185
P-glycoprotein substrateNon-substrate0.7632
P-glycoprotein inhibitor INon-inhibitor0.5423
P-glycoprotein inhibitor IIInhibitor0.5596
Renal organic cation transporterNon-inhibitor0.866
CYP450 2C9 substrateNon-substrate0.6378
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.5439
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 substrateInhibitor0.5752
CYP450 2D6 substrateNon-inhibitor0.9231
CYP450 2C19 substrateNon-inhibitor0.9026
CYP450 3A4 substrateNon-inhibitor0.5968
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5233
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.7995
BiodegradationNot ready biodegradable0.9881
Rat acute toxicity2.7753 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9469
hERG inhibition (predictor II)Non-inhibitor0.892
Pharmacoeconomics
Manufacturers
  • Sanofi aventis us llc
  • Novartis pharmaceuticals corp
  • Ivax pharmaceuticals inc
  • Mutual pharmaceutical co inc
  • Sandoz inc
  • Watson laboratories inc
Packagers
Dosage formsNot Available
Prices
Unit descriptionCostUnit
Phenylbutazone powder1.16USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point105 °CPhysProp
water solubility47.5 mg/L (at 30 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP3.16SANGSTER (1994)
logS-3.81ADME Research, USCD
pKa4.5SERJEANT,EP & DEMPSEY,B (1979)
Predicted Properties
PropertyValueSource
Water Solubility0.144 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity88.76 m3·mol-1ChemAxon
Polarizability34.15 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (9.03 KB)
SpectraNot Available
References
Synthesis Reference

Dieter Rahtz, Henning Koch, Erich Gerhards, “Hydroxy phenylbutazone derivatives and their preparation.” U.S. Patent US3968219, issued January, 1971.

US3968219
General ReferenceNot Available
External Links
ATC CodesM01AA01M02AA01
AHFS Codes
  • 28:08.04.92
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (73.1 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Prostaglandin G/H synthase 2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Prostaglandin G/H synthase 2 P35354 Details

References:

  1. Arifah AK, Lees P: Pharmacodynamics and pharmacokinetics of phenylbutazone in calves. J Vet Pharmacol Ther. 2002 Aug;25(4):299-309. Pubmed
  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
  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
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Prostacyclin synthase

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Prostacyclin synthase Q16647 Details

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
  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
  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
  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
  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

3. Prostaglandin G/H synthase 1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Prostaglandin G/H synthase 1 P23219 Details

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. Epub 2009 Oct 20. Pubmed
  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
  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

Enzymes

1. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  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. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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. Epub 2009 Nov 24. Pubmed

Transporters

1. Solute carrier family 22 member 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 6 Q4U2R8 Details

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
  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
  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

2. Solute carrier family 22 member 8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 8 Q8TCC7 Details

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

3. Solute carrier family 22 member 11

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 11 Q9NSA0 Details

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

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12