PHENYLBUTAZONE PIPERAZINE

US Previously Marketed

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H20N2O2.C4H10N2
Molecular Weight	394.5099
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C1CNCCN1.CCCCC2C(=O)N(N(C2=O)C3=CC=CC=C3)C4=CC=CC=C4

InChI

InChIKey=HWGAOXKGTHUMFZ-UHFFFAOYSA-N

InChI=1S/C19H20N2O2.C4H10N2/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;1-2-6-4-3-5-1/h4-13,17H,2-3,14H2,1H3;5-6H,1-4H2

HIDE SMILES / InChI

Molecular Formula	C4H10N2
Molecular Weight	86.1356
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C19H20N2O2
Molecular Weight	308.3743
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/796939 | https://www.ncbi.nlm.nih.gov/pubmed/14927431

Phenylbutazone is an anti-inflammatory drug, which binds to and inactivates cyclooxygenases and prostacyclin synthase through peroxide (H2O2) mediated deactivation. The reduced production of prostaglandin leads to reduced inflammation of the surrounding tissues. Phenylbutazone was marked under the brand name butazolidin for the treatment rheumatoid arthritis and gout, but then this usage was discontinued. In addition, phenylbutazone is used in UK for the treatment of ankylosing spondylitis, but only in those cases, when other therapies are unsuitable.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Prostacyclin synthase 4 Target ID: Q16647 Gene ID: 5740.0 Gene Symbol: PTGIS Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/3917545	Inhibitor 8504
Cyclooxygenase 89 Target ID: CHEMBL2094253 Sources: https://www.ncbi.nlm.nih.gov/pubmed/809810	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Ankylosing spondylitis 33 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12381510	Primary	Approved 8583	Unknown Approved Use Unknown
Gout 28 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14927431	Palliative	Approved 8583	BUTAZOLIDIN Approved Use Unknown
Rheumatoid arthritis 320 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14927431	Palliative	Approved 8583	BUTAZOLIDIN Approved Use Unknown

Doses

Dose	Population	Adverse events
8 g single, oral Overdose Dose: 8 g Route: oral Route: single Dose: 8 g Sources: https://pubmed.ncbi.nlm.nih.gov/7427601	healthy, 17 years Health Status: healthy Age Group: 17 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/7427601	Other AEs: Jaundice, Renal disorder NOS... Other AEs: Jaundice Renal disorder NOS Sources: https://pubmed.ncbi.nlm.nih.gov/7427601
800 mg 1 times / day multiple, oral Highest studied dose Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3907678	unhealthy, 52.8 years (range: 24-89 years) Health Status: unhealthy Age Group: 52.8 years (range: 24-89 years) Sources: https://pubmed.ncbi.nlm.nih.gov/3907678	Other AEs: Rash, Dyspepsia... Other AEs: Rash (1 patient) Dyspepsia (1 patient) Constipation (2 patients) Sleepiness (1 patient) Irritability (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/3907678

AEs

AE	Significance	Dose	Population
Jaundice		8 g single, oral Overdose Dose: 8 g Route: oral Route: single Dose: 8 g Sources: https://pubmed.ncbi.nlm.nih.gov/7427601	healthy, 17 years Health Status: healthy Age Group: 17 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/7427601
Renal disorder NOS		8 g single, oral Overdose Dose: 8 g Route: oral Route: single Dose: 8 g Sources: https://pubmed.ncbi.nlm.nih.gov/7427601	healthy, 17 years Health Status: healthy Age Group: 17 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/7427601
Dyspepsia	1 patient	800 mg 1 times / day multiple, oral Highest studied dose Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3907678	unhealthy, 52.8 years (range: 24-89 years) Health Status: unhealthy Age Group: 52.8 years (range: 24-89 years) Sources: https://pubmed.ncbi.nlm.nih.gov/3907678
Irritability	1 patient	800 mg 1 times / day multiple, oral Highest studied dose Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3907678	unhealthy, 52.8 years (range: 24-89 years) Health Status: unhealthy Age Group: 52.8 years (range: 24-89 years) Sources: https://pubmed.ncbi.nlm.nih.gov/3907678
Rash	1 patient	800 mg 1 times / day multiple, oral Highest studied dose Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3907678	unhealthy, 52.8 years (range: 24-89 years) Health Status: unhealthy Age Group: 52.8 years (range: 24-89 years) Sources: https://pubmed.ncbi.nlm.nih.gov/3907678
Sleepiness	1 patient	800 mg 1 times / day multiple, oral Highest studied dose Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3907678	unhealthy, 52.8 years (range: 24-89 years) Health Status: unhealthy Age Group: 52.8 years (range: 24-89 years) Sources: https://pubmed.ncbi.nlm.nih.gov/3907678
Constipation	2 patients	800 mg 1 times / day multiple, oral Highest studied dose Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3907678	unhealthy, 52.8 years (range: 24-89 years) Health Status: unhealthy Age Group: 52.8 years (range: 24-89 years) Sources: https://pubmed.ncbi.nlm.nih.gov/3907678

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1087	inhibitor 2438

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT1 725 OAT3 747 OAT4 150 MRP4 290 BCRP 910 MRP2 499 UGT1A6 136

Drug as perpetrator

Target	Modality	Activity
MRP2 625	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17578901/ Page: 5.0	no
BCRP 985	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17578901/ Page: 5.0	partial
CYP2C9 2497	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/3355588/	yes [Ki 11 uM]
MRP4 345	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17578901/ Page: 5.0	yes [Ki 354 uM]
OAT3 749	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17578901/ Page: 5.0	yes [Ki 6.82 uM]
OAT1 730	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17578901/ Page: 5.0	yes [Ki 71.6 uM]
CYP3A4 2633	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/10219967/	yes
OAT4 150	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/12130730/ Page: 1.0	yes
UGT1A6 171	inhibitor 4027 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067388/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:48574	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:48574
ChemicalBook	CB0370134	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0370134
eMolecules	27523332	https://www.emolecules.com/cgi-bin/more?vid=27523332
eMolecules	593834	https://www.emolecules.com/cgi-bin/more?vid=593834
MolPort	MolPort-001-783-564	https://www.molport.com/shop/molecule-link/MolPort-001-783-564
Selleck Chemicals	Phenylbutazone(Butazolidin)	http://www.selleckchem.com/products/Phenylbutazone(Butazolidin).html
ZINC	ZINC000100004227	http://zinc15.docking.org/substances/ZINC000100004227

PubMed

Title	Date	PubMed
Development of an in vitro reporter gene assay to assess xenobiotic induction of the human CYP3A4 gene.	1998-03-26	9512926
Efficacy of anticancer alkylphosphocholines in Trypanosoma brucei subspecies.	1997-04-15	9107362
Cancer chemopreventive activity of resveratrol, a natural product derived from grapes.	1997-01-10	8985016
Inhibition of tolbutamide 4-methylhydroxylation by a series of non-steroidal anti-inflammatory drugs in V79-NH cells expressing human cytochrome P4502C10.	1996-12	9004453
Antiinflammatory 4,5-diarylpyrroles. 2. Activity as a function of cyclooxygenase-2 inhibition.	1995-09-29	7562922
Misuse of veterinary phenylbutazone.	1995-06-12	7763130
Long-term exposure to the anti-inflammatory agent phenylbutazone induces kidney tumors in rats and liver tumors in mice.	1995-03	7744695
Aplastic anemia induced by an adulterated herbal medication.	1995	7650772
Antrafenine: anti-inflammatory activity with respect to oedema and leucocyte infiltration in the rat.	1984-02	6608864
Phenylbutazone nephrotoxicity--a light and electron microscopic study.	1983-12	6668168
[Kidney damage after treatment with butapyrazole].	1983-11-15	6675297
Renal medullary crest necrosis associated with phenylbutazone therapy in horses.	1983-11	6649337
Effects of large doses of phenylbutazone administration to horses.	1983-05	6869982
Phenylbutazone associated glomerulonephritis. Glomerulonephritis and fever.	1982-12	6130055
Sialadenitis and systemic reaction associated with phenylbutazone.	1982-06	6214246
Animal experiments on the safety pharmacology of lofexidine.	1982	6890367
Phenylbutazone liver injury: a clinical-pathologic survey of 23 cases and review of the literature.	1981-05-01	7286906
Acute nephrotic syndrome with reversible renal failure after phenylbutazone.	1981-03-21	6781669
Intrahepatic cholestasis induced by phenylbutazone.	1981	7333419
Phenylbutazone-induced blood dyscrasias suspected in three dogs.	1980-09-13	7257098
Use of phenylbutazone in sports medicine: understanding the risks.	1980-07-01	7053221
Exacerbation of phenylbutazone-related renal failure by indomethacin.	1978-11	718323
Interstitial nephritis in a case of phenylbutazone hypersensitivity.	1978-05-20	647258
Drug-related gustatory disorders.	1978-01-01	623418
Granulomas and cholestatic--hepatocellular injury associated with phenylbutazone. Report of two cases.	1977-07	879127
Development of a lymphocytic lymphoma during immunosuppressive therapy with azathioprine for systemic lupus erythematosus with renal involvement induced by phenylbutazone.	1977-07	577907
Association of renal papillary necrosis and ankylosing spondylitis.	1977-05	861066
Aplastic anemia from veterinary phenylbutazone.	1976-08-30	989582
Further studies of the acute effects of phenylbutazone, oxyphenbutazone and indomethacin on the rat kidney.	1976-04	972771
Clinical evaluation of ketoprofen (Orudis) in rheumatoid arthritis. Results of a multi-centre, double-blind, cross-over trial against phenylbutazone.	1976	790547
Double-bind cross-over tiral of flurbiprofen and phenylbutazone in ankylosing spondylitis.	1974-11-30	4611579
Letter: Idiosyncrasy to phenothiazines in phenylbutazone-associated aplastic anaemia.	1974-10-05	4425837
Renal and gastric lesions after phenylbutazone and indomethacin in the rat.	1974-10	4548752
Proceedings: A pharmacokinetic study of phenylbutazone-associated hypoplastic anaemia.	1974-09	4415226
Aspirin and the kidney. New Zealand Rheumatism Association Study.	1974-03-30	4821007
[Primary cardiac involvement and painful salivary gland enlargement due to phenylbutazone].	1974-03-01	4830208
[Acute renal insufficiency following butapyrazole treatment in the course of plasmatic cell leukemia (author's transl)].	1973	4779657
Papillary necrosis following phenylbutazone ingestion.	1971-09	5569932
[Allergo-toxic disturbances of the heart muscle with congestive heart failure as a result of parenteral treatment with phenylbutazone].	1971-02	5546848
Treatment of aplastic anemia with nandrolone decanoate.	1970-12	5485118
Mefanamic acid-induced haemolytic anaemia.	1970-05-02	5420190
Rheumatoid arthritis: comparison of treatment with monophenylbutazone and phenylbutazone.	1969-12-27	4903691
[A fatal pathological condition with hyperglobulinemic purpura and polymyositis after phenylbutazone].	1968-11-15	5755571
Probenecid, nephrotic syndrome, and renal failure.	1968-05	5655316
Phenylbutazone anuria.	1967-12	6060746
Bone marrow depression induced by chloramphenicol or phenylbutazone. Leukemia and other sequelae.	1967-09-11	6071896
Nephrotic syndrome caused by probenecid.	1967-01-02	6071127
[The renal incidents of phenylbutazone].	1966-12-03	5924165
[Renal complications following phenylbutazone treatment].	1966-05-19	5974146
Phenylbutazone-induced pericarditis.	1965-10-02	5825420

Patents

Sample Use Guides

In Vivo Use Guide

300 mg daily for 4 weeks

Route of Administration: Oral

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Mon Mar 31 19:31:30 GMT 2025` Edited by `admin` on `Mon Mar 31 19:31:30 GMT 2025`
Record UNII	0J1026H8UB
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PHENYLBUTAZONE-PIPERAZINE

Preferred Name

English

PHENYLBUTAZONE PIPERAZINE

Common Name

English

PYRASANONE

Common Name

English

PHENYLBUTAZONE PIPERAZINE SALT [MI]

Common Name

English

3,5-PYRAZOLIDINEDIONE, 4-BUTYL-1,2-DIPHENYL-, COMPD. WITH PIPERAZINE (1:1)

Systematic Name

English

PYRAZINOBUTAZONE

Common Name

English

Phenylbutazone-piperazine [WHO-DD]

Common Name

English

CARUDOL

Brand Name

English

Code System Code Type Description

FDA UNII

0J1026H8UB