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 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
[Renal complications following phenylbutazone treatment].	1966 May 19	5974146
Probenecid, nephrotic syndrome, and renal failure.	1968 May	5655316
[A fatal pathological condition with hyperglobulinemic purpura and polymyositis after phenylbutazone].	1968 Nov 15	5755571
Treatment of aplastic anemia with nandrolone decanoate.	1970 Dec	5485118
[Acute renal insufficiency following butapyrazole treatment in the course of plasmatic cell leukemia (author's transl)].	1973	4779657
Acetanilide oxidation in phenylbutazone-associated hypoplastic anaemia.	1974 Aug 3	4411815
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
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
Phenylbutazone and the horse--a review.	1977 Jul	330156
[Macroscopic hematuria during treatment with phenylbutazone derivatives. Positive lymphocyte transformation test for these drugs. Two cases in children].	1977 Oct	16211908
Renal papillary necrosis associated with indomethacin and phenylbutazone treated rheumatoid arthritis.	1978 Apr	277165
[Acute interstitial nephritis with oliguric renal failure following phenylbutazone medication].	1978 Apr 1	147510
Confusion associated with cimetidine.	1979 Dec 1	316351
Acute nephrotic syndrome with reversible renal failure after phenylbutazone.	1981 Mar 21	6781669
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
[Kidney damage after treatment with butapyrazole].	1983 Nov 15	6675297
[Nephrotic syndrome and acute interstitial nephritis after phenylbutazone].	1985 Nov 2	2934808
Drug-induced hepatitis associated with anticytoplasmic organelle autoantibodies.	1985 Sep-Oct	4029887
Differential effects of non-steroidal anti-inflammatory drugs on seizures produced by pilocarpine in rats.	1988 Oct 18	3191389
Aplastic anemia induced by an adulterated herbal medication.	1995	7650772
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
A reporter gene assay to assess the molecular mechanisms of xenobiotic-dependent induction of the human CYP3A4 gene in vitro.	1999 Mar	10219967
Immunomodulatory effect of nonsteroidal anti-inflammatory drugs (NSAIDs) at the clinically available doses.	2007 Jan	17328244
Characterization of UDP-glucuronosyltransferases involved in glucuronidation of diethylstilbestrol in human liver and intestine.	2012 Dec 17	23126256
FDA-approved drugs and other compounds tested as inhibitors of human glutathione transferase P1-1.	2013 Sep 5	23769903
Phenylbutazone Oxidation via Cu,Zn-SOD Peroxidase Activity: An EPR Study.	2015 Jul 20	26090772

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 `Fri Dec 15 19:02:51 GMT 2023` Edited by `admin` on `Fri Dec 15 19:02:51 GMT 2023`
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