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 8146
Cyclooxygenase 89 Target ID: CHEMBL2094253 Sources: https://www.ncbi.nlm.nih.gov/pubmed/809810	Inhibitor 8146

Conditions

Condition	Modality	Highest Phase	Product
Ankylosing spondylitis 33 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12381510	Primary	Approved 8307	Unknown Approved Use Unknown
Gout 26 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14927431	Palliative	Approved 8307	BUTAZOLIDIN Approved Use Unknown
Rheumatoid arthritis 310 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14927431	Palliative	Approved 8307	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 753	inhibitor 1695

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT1 584 OAT3 625 OAT4 145 MRP4 202 BCRP 678 MRP2 363 UGT1A6 107

Drug as perpetrator

Target	Modality	Activity
MRP2 452	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/17578901/ Page: 5.0	no
BCRP 751	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/17578901/ Page: 5.0	partial
CYP2C9 1747	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/3355588/	yes [Ki 11 uM]
MRP4 235	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/17578901/ Page: 5.0	yes [Ki 354 uM]
OAT3 627	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/17578901/ Page: 5.0	yes [Ki 6.82 uM]
OAT1 588	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/17578901/ Page: 5.0	yes [Ki 71.6 uM]
CYP3A4 1857	inducer 1515 Sources: https://pubmed.ncbi.nlm.nih.gov/10219967/	yes
OAT4 145	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/12130730/ Page: 1.0	yes
UGT1A6 139	inhibitor 3185 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
[Vasculitis allergica cutis caused by phenylbutazone].	1966	4224583
Nephrotic syndrome caused by probenecid.	1967 Jan 2	6071127
Rheumatoid arthritis: comparison of treatment with monophenylbutazone and phenylbutazone.	1969 Dec 27	4903691
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
[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
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
Granulomas and cholestatic--hepatocellular injury associated with phenylbutazone. Report of two cases.	1977 Jul	879127
Phenylbutazone and the horse--a review.	1977 Jul	330156
Association of renal papillary necrosis and ankylosing spondylitis.	1977 May	861066
[Macroscopic hematuria during treatment with phenylbutazone derivatives. Positive lymphocyte transformation test for these drugs. Two cases in children].	1977 Oct	16211908
Interstitial nephritis in a case of phenylbutazone hypersensitivity.	1978 May 20	647258
Confusion associated with cimetidine.	1979 Dec 1	316351
Use of phenylbutazone in sports medicine: understanding the risks.	1980 Jul-Aug	7053221
Antrafenine: anti-inflammatory activity with respect to oedema and leucocyte infiltration in the rat.	1984 Feb	6608864
Phenylbutazone-induced systemic vasculitis with crescentic glomerulonephritis.	1985 Apr	3157355
[Nephrotic syndrome and acute interstitial nephritis after phenylbutazone].	1985 Nov 2	2934808
Drug-induced hepatitis associated with anticytoplasmic organelle autoantibodies.	1985 Sep-Oct	4029887
Strain-related susceptibility to nephrotoxicity induced by aspirin and phenylbutazone in rats.	1986	3764320
Risks of agranulocytosis and aplastic anemia. A first report of their relation to drug use with special reference to analgesics. The International Agranulocytosis and Aplastic Anemia Study.	1986 Oct 3	3747087
[Hepatic lesions induced by drugs. Report of 26 cases].	1987	3442185
Dermatomyositis-like syndrome associated with phenylbutazone therapy.	1987 Apr	3599016
Diagnosis of antibody-mediated drug allergy. Pyrazolinone and pyrazolidinedione cross-reactivity relationships.	1987 Nov	3425858
Differential effects of non-steroidal anti-inflammatory drugs on seizures produced by pilocarpine in rats.	1988 Oct 18	3191389
Anti-inflammatory activity and sub-acute toxicity of artemetin.	1990 Feb	2356241
Misuse of veterinary phenylbutazone.	1995 Jun 12	7763130
Efficacy of anticancer alkylphosphocholines in Trypanosoma brucei subspecies.	1997 Apr 15	9107362
Development of an in vitro reporter gene assay to assess xenobiotic induction of the human CYP3A4 gene.	1997 Oct-Dec	9512926
Non-steroidal anti-inflammatory drugs inhibit the expression of cytokines and induce HSP70 in human monocytes.	1999 May	10328874
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.	2004 Dec 9	15489888
Synthesis of biologically active N-methyl derivatives of amidines and cyclized five-membered products of amidines with oxalyl chloride.	2008 Dec	18022734
Identification of genomic biomarkers for concurrent diagnosis of drug-induced renal tubular injury using a large-scale toxicogenomics database.	2009 Nov 9	19761811
Toxicogenomic biomarkers for renal papillary injury in rats.	2013 Jan 7	23142791
Use of micropatterned cocultures to detect compounds that cause drug-induced liver injury in humans.	2013 Mar	23152190
Genomic biomarkers for cardiotoxicity in rats as a sensitive tool in preclinical studies.	2013 Oct	23558518
FDA-approved drugs and other compounds tested as inhibitors of human glutathione transferase P1-1.	2013 Sep 5	23769903

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 `Sat Dec 17 01:54:00 UTC 2022` Edited by `admin` on `Sat Dec 17 01:54:00 UTC 2022`
Record UNII	0J1026H8UB
Record Status	`Validated (UNII)`
Record Version

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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