SULFINPYRAZONE

Details

Stereochemistry	RACEMIC
Molecular Formula	C23H20N2O3S
Molecular Weight	404.482
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[O-][S+](CCC1C(=O)N(N(C1=O)C2=CC=CC=C2)C3=CC=CC=C3)C4=CC=CC=C4

InChI

InChIKey=MBGGBVCUIVRRBF-UHFFFAOYSA-N

InChI=1S/C23H20N2O3S/c26-22-21(16-17-29(28)20-14-8-3-9-15-20)23(27)25(19-12-6-2-7-13-19)24(22)18-10-4-1-5-11-18/h1-15,21H,16-17H2

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB01138
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/pro/anturane.html

Sulfinpyrazone was approved by the U.S. Food and Drug Administration (FDA) on May 13, 1959. It was developed and marketed as Anturane® by Novartis. Sulfinpyrazone is an oral uricosuric agent (pyrazolone derivative) used to treat chronic or intermittent gouty arthritis. Sulfinpyrazone competitively inhibits the reabsorption of uric acid at the proximal convoluted tubule, thereby facilitating urinary excretion of uric acid and decreasing plasma urate concentrations. This is likely done through inhibition of the urate anion transporter (hURAT1) as well as the human organic anion transporter 4 (hOAT4). Sulfinpyrazone is not intended for the treatment of acute attacks because it lacks therapeutically useful analgesic and anti-inflammatory effects. Sulfinpyrazone and its sulfide metabolite possess COX inhibitory effects. Sulfinpyrazone has also been shown to be a UDP-glucuronsyltransferase inhibitor and a very potent CYP2C9 inhibitor. Sulfinpyrazone is also known to be a cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor as well as an inhibitor of several multridrug resistance proteins (MRPs). Branded and generic forms of sulfinpyrazone have been discontinued in the US.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Canalicular multispecific organic anion transporter 1 21 Target ID: CHEMBL5748 Sources: http://www.drugbank.ca/drugs/DB01138	Modulator 828
Multidrug resistance-associated protein 1 15 Target ID: CHEMBL3004 Sources: http://www.drugbank.ca/drugs/DB01138	Inhibitor 8297
Multidrug resistance-associated protein 5 1 Target ID: CHEMBL2046258 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10840050	Inhibitor 8297
Solute carrier family 22 member 12 10 Target ID: CHEMBL6120 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17325024	Inhibitor 8297	100.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Gouty arthritis 4 Sources: https://www.drugs.com/pro/anturane.html	Primary		Approved 8429	Anturane Approved Use Anturane is indicated for the treatment of: Chronic gouty arthritis Intermittent gouty arthritis Launch Date 1959

C_max

Value	Dose	Analyte	Population
13.4 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3987792/	400 mg 2 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	SULFINPYRAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
26 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3987792/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	SULFINPYRAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2.2 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3987792/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	SULFINPYRAZONE SULFONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3987792/	400 mg 2 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	SULFINPYRAZONE SULFONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
53 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3987792/	400 mg 2 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	SULFINPYRAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
191.9 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7059415/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	SULFINPYRAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
116 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3987792/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	SULFINPYRAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
79.6 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7059415/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	SULFINPYRAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
13.4 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3987792/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	SULFINPYRAZONE SULFONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
9.2 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3987792/	400 mg 2 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	SULFINPYRAZONE SULFONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
16.5 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7059415/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	SULFINPYRAZONE SULFONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
5.7 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7059415/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	SULFINPYRAZONE SULFONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
9.96 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3987792/	400 mg 2 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	SULFINPYRAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
4.17 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7059415/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	SULFINPYRAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3987792/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	SULFINPYRAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
3.79 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7059415/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	SULFINPYRAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3987792/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	SULFINPYRAZONE SULFONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
3.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3987792/	400 mg 2 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	SULFINPYRAZONE SULFONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
3.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7059415/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	SULFINPYRAZONE SULFONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
1000 mg single, oral Overdose Dose: 1000 mg Route: oral Route: single Dose: 1000 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1548318/	healthy, 24 n = 1 Health Status: healthy Age Group: 24 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1548318/	Other AEs: Acute renal failure... Other AEs: Acute renal failure Sources: https://pubmed.ncbi.nlm.nih.gov/1548318/
1000 mg multiple, oral (max) Recommended Dose: 1000 mg Route: oral Route: multiple Dose: 1000 mg Sources: https://www.aapharma.ca/downloads/en/PIL/2016/Sulfinpyrazone-PM.pdf Page: p.2	unhealthy Health Status: unhealthy Condition: Thrombosis Sources: https://www.aapharma.ca/downloads/en/PIL/2016/Sulfinpyrazone-PM.pdf Page: p.2	Other AEs: Acute renal failure... Other AEs: Acute renal failure (low incidence) Sources: https://www.aapharma.ca/downloads/en/PIL/2016/Sulfinpyrazone-PM.pdf Page: p.2
400 mg 2 times / day multiple, oral (max) Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://www.aapharma.ca/downloads/en/PIL/2016/Sulfinpyrazone-PM.pdf Page: p.4	unhealthy Health Status: unhealthy Condition: Gouty arthritis Sources: https://www.aapharma.ca/downloads/en/PIL/2016/Sulfinpyrazone-PM.pdf Page: p.4	Disc. AE: Skin rash... AEs leading to discontinuation/dose reduction: Skin rash (rare) Sources: https://www.aapharma.ca/downloads/en/PIL/2016/Sulfinpyrazone-PM.pdf Page: p.4

AEs

AE	Significance	Dose	Population
Acute renal failure		1000 mg single, oral Overdose Dose: 1000 mg Route: oral Route: single Dose: 1000 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1548318/	healthy, 24 n = 1 Health Status: healthy Age Group: 24 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1548318/
Acute renal failure	low incidence	1000 mg multiple, oral (max) Recommended Dose: 1000 mg Route: oral Route: multiple Dose: 1000 mg Sources: https://www.aapharma.ca/downloads/en/PIL/2016/Sulfinpyrazone-PM.pdf Page: p.2	unhealthy Health Status: unhealthy Condition: Thrombosis Sources: https://www.aapharma.ca/downloads/en/PIL/2016/Sulfinpyrazone-PM.pdf Page: p.2
Skin rash	rare Disc. AE	400 mg 2 times / day multiple, oral (max) Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://www.aapharma.ca/downloads/en/PIL/2016/Sulfinpyrazone-PM.pdf Page: p.4	unhealthy Health Status: unhealthy Condition: Gouty arthritis Sources: https://www.aapharma.ca/downloads/en/PIL/2016/Sulfinpyrazone-PM.pdf Page: p.4

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781 inhibitor 1587	inhibitor 1767

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 911 MRP4 204 MRP5 22 MRP1 106 MRP2 383 UGT1A1 204 UGT1A3 84 UGT1A4 77 UGT1A6 108 UGT1A7 21 UGT1A8 36 UGT1A9 116 UGT1A10 32 UGT2B7 146 UGT2B15 64		CYP2B6 547

Drug as perpetrator

Target	Modality	Activity
CYP2B6 1001	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/14977870/	weak
MRP5 48	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16337112/ Page: 6.0	yes [IC50 103 uM]
UGT1A9 121	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16381668/ Page: 6.0	yes [IC50 11 uM]
UGT1A8 48	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16381668/ Page: 6.0	yes [IC50 158 uM]
UGT1A7 23	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16381668/ Page: 6.0	yes [IC50 16 uM]
UGT1A6 141	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16381668/ Page: 6.0	yes [IC50 187 uM]
UGT1A3 93	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16381668/ Page: 6.0	yes [IC50 267 uM]
UGT2B7 157	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16381668/ Page: 6.0	yes [IC50 2741 uM]
UGT2B15 64	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16381668/ Page: 6.0	yes [IC50 402 uM]
MRP4 238	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12695538/ Page: 9.0	yes [IC50 420 uM]
UGT1A1 254	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16381668/ Page: 6.0	yes [IC50 46 uM]
UGT1A10 41	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16381668/ Page: 6.0	yes [IC50 58 uM]
UGT1A4 80	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16381668/ Page: 6.0	yes [IC50 651 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/7587949/	yes [Ki 230 uM]
CYP2C8 965	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/11996015/ Page: 77.0	yes
CYP3A4 1925	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/10219967/ Page: 1.0	yes
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/11996015/ Page: 184.0	yes
MRP1 172	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084506/	yes
MRP2 475	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084506/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:9342	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:9342
ChemicalBook	CB2122351	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB2122351
MolPort	MolPort-003-666-286	https://www.molport.com/shop/molecule-link/MolPort-003-666-286
eMolecules	544393	https://www.emolecules.com/cgi-bin/more?vid=544393

PubMed

Title	Date	PubMed
Are agents affecting platelet functions clinically useful?	1976 Dec	795299
Acute myelomonocytic leukaemia and multiple myeloma after sulphinpyrazone and colchicine treatment of gout.	1976 Jul 10	1064465
Abnormalities of urinary sediment and renal failure following sulfinpyrazone therapy.	1976 Sep	962450
[Acute renal failure induced by sulfinpyrazone (author's transl)].	1981	7301034
Acute renal dysfunction due to sulfinpyrazone therapy in post-myocardial infarction cardiomegaly: reversible hypersensitive interstitial nephritis.	1981 Aug	7258104
Effects of sulfinpyrazone, aspirin and propranolol on the isoproterenol-induced myocardial necrosis.	1981 Jul	6272002
Non oliguric acute renal failure after treatment with sulfinpyrazone.	1982 May	7094443
Sulfinpyrazone-associated acute renal failure.	1983 Jul	6883821
Decrease in renal function due to sulphinpyrazone treatment early after myocardial infarction.	1983 Mar	6340878
[Acute interstitial nephritis and kidney failure requiring dialysis after sulfinpyrazone therapy].	1984	6234742
Sulfinpyrazone: risk for renal insufficiency.	1984 Mar	6703838
[Acute tubulo-interstitial nephropathy associated with ingestion of sulfinpyrazone].	1985 Feb 23	3157154
Acute renal failure due to sulfinpyrazone.	1998 May	9587090
Essential requirements for substrate binding affinity and selectivity toward human CYP2 family enzymes.	2003 Jan 1	12464242
Functional expression of the multidrug resistance protein 1 in microglia.	2003 Oct	12893836
Glutathione S-transferase M1 and multidrug resistance protein 1 act in synergy to protect melanoma cells from vincristine effects.	2004 Apr	15044619
High-throughput screening with HyperCyt flow cytometry to detect small molecule formylpeptide receptor ligands.	2005 Jun	15964939
Prediction of CYP2C9-mediated drug-drug interactions: a comparison using data from recombinant enzymes and human hepatocytes.	2005 Nov	16081671
Use of immortalized human hepatocytes to predict the magnitude of clinical drug-drug interactions caused by CYP3A4 induction.	2006 Oct	16837568
In silico prediction of pregnane X receptor activators by machine learning approaches.	2007 Jan	17003167
Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11).	2013 Dec	24014644

Patents

Sample Use Guides

In Vivo Use Guide

Initial 200-400 mg daily in two divided doses, with meals or milk, gradually increasing when necessary to full maintenance dosage in one week. Maintenance 400 mg daily, given in two divided doses, as above. This dosage may be increased to 800 mg daily, if necessary, and may sometimes be reduced to as low as 200 mg daily after the blood urate level has been controlled.

Route of Administration: Oral

In Vitro Use Guide

Sulfinpyrazone (2.5 mM) inhibited the MRP5-mediated PMEA efflux from resistant 293/MRP5 cells

Name

Type

Language

SULFINPYRAZONE

Official Name

English

sulfinpyrazone [INN]

Common Name

English

SULFINPYRAZONE [VANDF]

Common Name

English

ANTURANE

Brand Name

English

SULFINPYRAZONE [MI]

Common Name

English

NSC-75925

Code

English

SULFINPYRAZONE [EP IMPURITY]

Common Name

English

1,2-Diphenyl-4-[2-(phenylsulfinyl)ethyl]-3,5-pyrazolidinedione

Systematic Name

English

SULFINPYRAZONE [EP MONOGRAPH]

Common Name

English

3,5-PYRAZOLIDINEDIONE, 1,2-DIPHENYL-4-(2-(PHENYLSULFINYL)ETHYL)-

Systematic Name

English

SULFINPYRAZONE [JAN]

Common Name

English

Sulfinpyrazone [WHO-DD]

Common Name

English

SULPHINPYRAZONE

Common Name

English

SULFINPYRAZONE [MART.]

Common Name

English

SULFINPYRAZONE [USP-RS]

Common Name

English

SULFINPYRAZONE [ORANGE BOOK]

Common Name

English

SULFINPYRAZONE [USP IMPURITY]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C921