SULFINPYRAZONE

US Previously Marketed

Details

Stereochemistry	RACEMIC
Molecular Formula	C23H20N2O3S
Molecular Weight	404.4834
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

c1ccc(cc1)N2C(=O)C(CCS(=O)c3ccccc3)C(=O)N2c4ccccc4

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

Molecular Formula	C23H20N2O3S
Molecular Weight	404.4834
Charge	0
Count

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

Description
Sources: http://www.drugbank.ca/drugs/DB01138
Curator's Comment:: 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	Condition	Potency
Canalicular multispecific organic anion transporter 1 19 Target ID: CHEMBL5748 Sources: http://www.drugbank.ca/drugs/DB01138	Modulator 777	Gouty arthritis
Multidrug resistance-associated protein 1 15 Target ID: CHEMBL3004 Sources: http://www.drugbank.ca/drugs/DB01138	Inhibitor 7701	Gouty arthritis
Multidrug resistance-associated protein 5 1 Target ID: CHEMBL2046258 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10840050	Inhibitor 7701
Solute carrier family 22 member 12 9 Target ID: CHEMBL6120 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17325024	Inhibitor 7701	Gouty arthritis	100 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Gouty arthritis 4 Sources: https://www.drugs.com/pro/anturane.html	Primary	Solute carrier family 22 member 12 Canalicular multispecific organic anion transporter 1 Multidrug resistance-associated protein 1	Approved 7997	Anturane Approved Use Anturane is indicated for the treatment of: Chronic gouty arthritis Intermittent gouty arthritis Launch Date -335836800000

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 Health Status: healthy Age Group: 24 Sex: M 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 Recommended Dose: 1000 mg Route: oral Route: multiple Dose: 1000 mg Sources: https://www.aapharma.ca/downloads/en/PIL/2016/Sulfinpyrazone-PM.pdf	unhealthy Health Status: unhealthy Sources: https://www.aapharma.ca/downloads/en/PIL/2016/Sulfinpyrazone-PM.pdf	Other AEs: Acute renal failure... Other AEs: Acute renal failure (low incidence) Sources: https://www.aapharma.ca/downloads/en/PIL/2016/Sulfinpyrazone-PM.pdf
400 mg 2 times / day multiple, oral 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	unhealthy Health Status: unhealthy Sources: https://www.aapharma.ca/downloads/en/PIL/2016/Sulfinpyrazone-PM.pdf	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

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 Health Status: healthy Age Group: 24 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/1548318/
Acute renal failure	low incidence	1000 mg multiple, oral Recommended Dose: 1000 mg Route: oral Route: multiple Dose: 1000 mg Sources: https://www.aapharma.ca/downloads/en/PIL/2016/Sulfinpyrazone-PM.pdf	unhealthy Health Status: unhealthy Sources: https://www.aapharma.ca/downloads/en/PIL/2016/Sulfinpyrazone-PM.pdf
Skin rash	rare Disc. AE	400 mg 2 times / day multiple, oral 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	unhealthy Health Status: unhealthy Sources: https://www.aapharma.ca/downloads/en/PIL/2016/Sulfinpyrazone-PM.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 657 inhibitor 1172	inhibitor 1318

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 761 MRP4 194 MRP5 21 MRP1 69 MRP2 341 UGT1A1 174 UGT1A3 76 UGT1A4 67 UGT1A6 94 UGT1A7 17 UGT1A8 29 UGT1A9 102 UGT1A10 26 UGT2B7 130 UGT2B15 56		CYP2B6 486

Drug as perpetrator

Target	Modality	Activity
CYP2B6 845	inducer 1333 Sources: https://pubmed.ncbi.nlm.nih.gov/14977870/	weak
MRP5 45	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/16337112/ Page: 6	yes [IC50 103 uM]
UGT1A9 107	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/16381668/ Page: 6	yes [IC50 11 uM]
UGT1A8 41	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/16381668/ Page: 6	yes [IC50 158 uM]
UGT1A7 19	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/16381668/ Page: 6	yes [IC50 16 uM]
UGT1A6 126	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/16381668/ Page: 6	yes [IC50 187 uM]
UGT1A3 82	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/16381668/ Page: 6	yes [IC50 267 uM]
UGT2B7 138	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/16381668/ Page: 6	yes [IC50 2741 uM]
UGT2B15 56	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/16381668/ Page: 6	yes [IC50 402 uM]
MRP4 226	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/12695538/ Page: 9	yes [IC50 420 uM]
UGT1A1 219	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/16381668/ Page: 6	yes [IC50 46 uM]
UGT1A10 35	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/16381668/ Page: 6	yes [IC50 58 uM]
UGT1A4 70	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/16381668/ Page: 6	yes [IC50 651 uM]
CYP2C9 1362	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/7587949/	yes [Ki 230 uM]
CYP2C8 810	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/11996015/ Page: 77	yes
CYP3A4 1462	inducer 1333 Sources: https://pubmed.ncbi.nlm.nih.gov/10219967/ Page: 1	yes
CYP3A4 1462	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/11996015/ Page: 184	yes
MRP1 129	inhibitor 2614 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084506/	yes
MRP2 421	inhibitor 2614 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
MolPort	MolPort-003-666-286	https://www.molport.com/shop/molecule-link/MolPort-003-666-286

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
[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
Sulphinpyrazone-induced acute renal failure.	1981 Feb 21	6781590
Sulfinpyrazone induced uric acid urolithiasis with acute renal failure.	1981 Jul	7249646
Effects of sulfinpyrazone, aspirin and propranolol on the isoproterenol-induced myocardial necrosis.	1981 Jul	6272002
Renal dysfunction due to anturan.	1981 Jul 9	7242573
Renal dysfunction due to anturane.	1981 Nov 5	7290123
Sulphinpyrazone--induced decrease in renal function: a review of reports with discussion of pathogenesis.	1982	6926346
Acute renal failure following sulfinpyrazone therapy.	1982 Apr	6954641
[Sulfinpyrazone-associated renal failure (author's transl)].	1982 Jul 9	7084072
Non oliguric acute renal failure after treatment with sulfinpyrazone.	1982 May	7094443
Transcoronary platelet thromboxane A2 formation without platelet trapping in patients with coronary stenosis-effect of sulphinpyrazone treatment.	1983 Dec 30	6665767
Sulfinpyrazone-associated acute renal failure.	1983 Jul	6883821
[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
Interaction of sulfonamide and sulfone compounds with Toxoplasma gondii dihydropteroate synthase.	1990 Feb	2298911
Comparison of furosemide and vinblastine secretion from cell lines overexpressing multidrug resistance protein (P-glycoprotein) and multidrug resistance-associated proteins (MRP1 and MRP2).	2002	11834888
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
Role of multidrug resistance protein 2 (MRP2, ABCC2) in alkylating agent detoxification: MRP2 potentiates glutathione S-transferase A1-1-mediated resistance to chlorambucil cytotoxicity.	2004 Jan	14569069
Regulation of CYP2B6 in primary human hepatocytes by prototypical inducers.	2004 Mar	14977870
Combined effects of GSTP1 and MRP1 in melanoma drug resistance.	2005 Jul 25	15999103
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
Morin (3,5,7,2',4'-pentahydroxyflavone) exhibits potent inhibitory actions on urate transport by the human urate anion transporter (hURAT1) expressed in human embryonic kidney cells.	2007 Jun	17325024
HepaRG cells as an in vitro model for evaluation of cytochrome P450 induction in humans.	2008 Jan	17954527
Interactions of urate transporter URAT1 in human kidney with uricosuric drugs.	2011 Feb	21272127
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

Route of Administration: Oral

In Vitro Use Guide

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

Substance Class	Chemical Created by `admin` on `Fri Jun 25 21:16:10 UTC 2021` Edited by `admin` on `Fri Jun 25 21:16:10 UTC 2021`
Record UNII	V6OFU47K3W
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SULFINPYRAZONE

Official Name

English

SULFINPYRAZONE [WHO-DD]

Common Name

English

SULFINPYRAZONE [INN]

Common Name

English

SULFINPYRAZONE [EP]

Common Name

English

SULFINPYRAZONE [USP]

Common Name

English

SULFINPYRAZONE [VANDF]

Common Name

English

ANTURANE

Brand Name

English

SULFINPYRAZONE [MI]

Common Name

English

NSC-75925

Code

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

SULPHINPYRAZONE

Common Name

English

SULFINPYRAZONE [MART.]

Common Name

English

SULFINPYRAZONE [USP-RS]

Common Name

English

SULFINPYRAZONE [ORANGE BOOK]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C921