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

Molecular Formula	C23H20N2O3S
Molecular Weight	404.482
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: 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 822
Multidrug resistance-associated protein 1 15 Target ID: CHEMBL3004 Sources: http://www.drugbank.ca/drugs/DB01138	Inhibitor 8228
Multidrug resistance-associated protein 5 1 Target ID: CHEMBL2046258 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10840050	Inhibitor 8228
Solute carrier family 22 member 12 10 Target ID: CHEMBL6120 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17325024	Inhibitor 8228	100.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Gouty arthritis 4 Sources: https://www.drugs.com/pro/anturane.html	Primary		Approved 8360	Anturane Approved Use Anturane is indicated for the treatment of: Chronic gouty arthritis Intermittent gouty arthritis Launch Date -3.35836807E11

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 768 inhibitor 1579	inhibitor 1752

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 901 MRP4 203 MRP5 22 MRP1 106 MRP2 367 UGT1A1 204 UGT1A3 84 UGT1A4 77 UGT1A6 108 UGT1A7 21 UGT1A8 36 UGT1A9 116 UGT1A10 32 UGT2B7 146 UGT2B15 64		CYP2B6 538

Drug as perpetrator

Target	Modality	Activity
CYP2B6 985	inducer 1542 Sources: https://pubmed.ncbi.nlm.nih.gov/14977870/	weak
MRP5 48	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/16337112/ Page: 6.0	yes [IC50 103 uM]
UGT1A9 121	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/16381668/ Page: 6.0	yes [IC50 11 uM]
UGT1A8 48	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/16381668/ Page: 6.0	yes [IC50 158 uM]
UGT1A7 23	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/16381668/ Page: 6.0	yes [IC50 16 uM]
UGT1A6 141	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/16381668/ Page: 6.0	yes [IC50 187 uM]
UGT1A3 93	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/16381668/ Page: 6.0	yes [IC50 267 uM]
UGT2B7 157	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/16381668/ Page: 6.0	yes [IC50 2741 uM]
UGT2B15 64	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/16381668/ Page: 6.0	yes [IC50 402 uM]
MRP4 237	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/12695538/ Page: 9.0	yes [IC50 420 uM]
UGT1A1 254	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/16381668/ Page: 6.0	yes [IC50 46 uM]
UGT1A10 41	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/16381668/ Page: 6.0	yes [IC50 58 uM]
UGT1A4 80	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/16381668/ Page: 6.0	yes [IC50 651 uM]
CYP2C9 1803	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/7587949/	yes [Ki 230 uM]
CYP2C8 955	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/11996015/ Page: 77.0	yes
CYP3A4 1909	inducer 1542 Sources: https://pubmed.ncbi.nlm.nih.gov/10219967/ Page: 1.0	yes
CYP3A4 1909	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/11996015/ Page: 184.0	yes
MRP1 172	inhibitor 3240 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084506/	yes
MRP2 459	inhibitor 3240 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
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
Acute renal failure secondary to sulfinpyrazone treatment after myocardial infarction.	1984	6738772
Interaction of sulfonamide and sulfone compounds with Toxoplasma gondii dihydropteroate synthase.	1990 Feb	2298911
Acute renal failure due to sulfinpyrazone.	1998 May	9587090
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
Combined effects of GSTP1 and MRP1 in melanoma drug resistance.	2005 Jul 25	15999103
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

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

Substance Class	Chemical Created by `admin` on `Thu Jul 06 01:57:30 UTC 2023` Edited by `admin` on `Thu Jul 06 01:57:30 UTC 2023`
Record UNII	V6OFU47K3W
Record Status	`Validated (UNII)`
Record Version

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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