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

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 8297
Cyclooxygenase 89 Target ID: CHEMBL2094253 Sources: https://www.ncbi.nlm.nih.gov/pubmed/809810	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Ankylosing spondylitis 33 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12381510	Primary	Approved 8429	Unknown Approved Use Unknown
Gout 28 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14927431	Palliative	Approved 8429	BUTAZOLIDIN Approved Use Unknown
Rheumatoid arthritis 316 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14927431	Palliative	Approved 8429	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 n = 1 Health Status: healthy Age Group: 17 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/7427601	Other AEs: Renal disorder NOS, Jaundice... Other AEs: Renal disorder NOS Jaundice 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 Condition: acute gouty arthritis 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 n = 1 Health Status: healthy Age Group: 17 years Sex: F Population Size: 1 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 n = 1 Health Status: healthy Age Group: 17 years Sex: F Population Size: 1 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 Condition: acute gouty arthritis 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 Condition: acute gouty arthritis 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 Condition: acute gouty arthritis 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 Condition: acute gouty arthritis 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 Condition: acute gouty arthritis Age Group: 52.8 years (range: 24-89 years) Sources: https://pubmed.ncbi.nlm.nih.gov/3907678

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781	inhibitor 1767

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT1 599 OAT3 642 OAT4 146 MRP4 204 BCRP 699 MRP2 383 UGT1A6 108

Drug as perpetrator

Target	Modality	Activity
MRP2 475	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17578901/ Page: 5.0	no
BCRP 773	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17578901/ Page: 5.0	partial
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/3355588/	yes [Ki 11 uM]
MRP4 238	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17578901/ Page: 5.0	yes [Ki 354 uM]
OAT3 644	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17578901/ Page: 5.0	yes [Ki 6.82 uM]
OAT1 603	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17578901/ Page: 5.0	yes [Ki 71.6 uM]
CYP3A4 1925	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/10219967/	yes
OAT4 146	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12130730/ Page: 1.0	yes
UGT1A6 141	inhibitor 3277 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
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
eMolecules	27523332	https://www.emolecules.com/cgi-bin/more?vid=27523332
eMolecules	593834	https://www.emolecules.com/cgi-bin/more?vid=593834

PubMed

Title	Date	PubMed
Phenylbutazone-induced pericarditis.	1965 Oct 2	5825420
[The renal incidents of phenylbutazone].	1966 Dec 3	5924165
[Renal complications following phenylbutazone treatment].	1966 May 19	5974146
Phenylbutazone anuria.	1967 Dec	6060746
Nephrotic syndrome caused by probenecid.	1967 Jan 2	6071127
Bone marrow depression induced by chloramphenicol or phenylbutazone. Leukemia and other sequelae.	1967 Sep 11	6071896
Probenecid, nephrotic syndrome, and renal failure.	1968 May	5655316
[A fatal pathological condition with hyperglobulinemic purpura and polymyositis after phenylbutazone].	1968 Nov 15	5755571
Rheumatoid arthritis: comparison of treatment with monophenylbutazone and phenylbutazone.	1969 Dec 27	4903691
Treatment of aplastic anemia with nandrolone decanoate.	1970 Dec	5485118
Mefanamic acid-induced haemolytic anaemia.	1970 May 2	5420190
[Allergo-toxic disturbances of the heart muscle with congestive heart failure as a result of parenteral treatment with phenylbutazone].	1971 Feb	5546848
Papillary necrosis following phenylbutazone ingestion.	1971 Sep	5569932
[Acute renal insufficiency following butapyrazole treatment in the course of plasmatic cell leukemia (author's transl)].	1973	4779657
[Primary cardiac involvement and painful salivary gland enlargement due to phenylbutazone].	1974 Mar 1	4830208
Aspirin and the kidney. New Zealand Rheumatism Association Study.	1974 Mar 30	4821007
Double-bind cross-over tiral of flurbiprofen and phenylbutazone in ankylosing spondylitis.	1974 Nov 30	4611579
Renal and gastric lesions after phenylbutazone and indomethacin in the rat.	1974 Oct	4548752
Letter: Idiosyncrasy to phenothiazines in phenylbutazone-associated aplastic anaemia.	1974 Oct 5	4425837
Proceedings: A pharmacokinetic study of phenylbutazone-associated hypoplastic anaemia.	1974 Sep	4415226
Clinical evaluation of ketoprofen (Orudis) in rheumatoid arthritis. Results of a multi-centre, double-blind, cross-over trial against phenylbutazone.	1976	790547
Further studies of the acute effects of phenylbutazone, oxyphenbutazone and indomethacin on the rat kidney.	1976 Apr	972771
Aplastic anemia from veterinary phenylbutazone.	1976 Aug 30	989582
Granulomas and cholestatic--hepatocellular injury associated with phenylbutazone. Report of two cases.	1977 Jul	879127
Development of a lymphocytic lymphoma during immunosuppressive therapy with azathioprine for systemic lupus erythematosus with renal involvement induced by phenylbutazone.	1977 Jul	577907
Association of renal papillary necrosis and ankylosing spondylitis.	1977 May	861066
Drug-related gustatory disorders.	1978 Jan-Feb	623418
Interstitial nephritis in a case of phenylbutazone hypersensitivity.	1978 May 20	647258
Exacerbation of phenylbutazone-related renal failure by indomethacin.	1978 Nov	718323
Use of phenylbutazone in sports medicine: understanding the risks.	1980 Jul-Aug	7053221
Phenylbutazone-induced blood dyscrasias suspected in three dogs.	1980 Sep 13	7257098
Intrahepatic cholestasis induced by phenylbutazone.	1981	7333419
Acute nephrotic syndrome with reversible renal failure after phenylbutazone.	1981 Mar 21	6781669
Phenylbutazone liver injury: a clinical-pathologic survey of 23 cases and review of the literature.	1981 May-Jun	7286906
Animal experiments on the safety pharmacology of lofexidine.	1982	6890367
Phenylbutazone associated glomerulonephritis. Glomerulonephritis and fever.	1982 Dec	6130055
Sialadenitis and systemic reaction associated with phenylbutazone.	1982 Jun	6214246
Phenylbutazone nephrotoxicity--a light and electron microscopic study.	1983 Dec	6668168
Effects of large doses of phenylbutazone administration to horses.	1983 May	6869982
Renal medullary crest necrosis associated with phenylbutazone therapy in horses.	1983 Nov	6649337
[Kidney damage after treatment with butapyrazole].	1983 Nov 15	6675297
Antrafenine: anti-inflammatory activity with respect to oedema and leucocyte infiltration in the rat.	1984 Feb	6608864
Aplastic anemia induced by an adulterated herbal medication.	1995	7650772
Misuse of veterinary phenylbutazone.	1995 Jun 12	7763130
Long-term exposure to the anti-inflammatory agent phenylbutazone induces kidney tumors in rats and liver tumors in mice.	1995 Mar	7744695
Antiinflammatory 4,5-diarylpyrroles. 2. Activity as a function of cyclooxygenase-2 inhibition.	1995 Sep 29	7562922
Inhibition of tolbutamide 4-methylhydroxylation by a series of non-steroidal anti-inflammatory drugs in V79-NH cells expressing human cytochrome P4502C10.	1996 Dec	9004453
Efficacy of anticancer alkylphosphocholines in Trypanosoma brucei subspecies.	1997 Apr 15	9107362
Cancer chemopreventive activity of resveratrol, a natural product derived from grapes.	1997 Jan 10	8985016
Development of an in vitro reporter gene assay to assess xenobiotic induction of the human CYP3A4 gene.	1997 Oct-Dec	9512926

Patents

Sample Use Guides

In Vivo Use Guide

300 mg daily for 4 weeks

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

PHENYLBUTAZONE PIPERAZINE

Common Name

English

PYRASANONE

Common Name

English

PHENYLBUTAZONE-PIPERAZINE

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