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

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	MOL RATIO 1 MOL RATIO (average)

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

Description

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	Modulator 846
Multidrug resistance-associated protein 1 15	Inhibitor 8,504
Multidrug resistance-associated protein 5 1	Inhibitor 8,504
Solute carrier family 22 member 12 10	Inhibitor 8,504	100.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Gouty arthritis 4	Primary		Approved 8,583	Anturane

C_max

Value	Dose	Analyte	Population
26 mg/L	400 mg single, oral	SULFINPYRAZONE plasma	Homo sapiens
13.4 mg/L	400 mg 2 times / day multiple, oral	SULFINPYRAZONE plasma	Homo sapiens
2.2 mg/L	400 mg single, oral	SULFINPYRAZONE SULFONE plasma	Homo sapiens
2 mg/L	400 mg 2 times / day multiple, oral	SULFINPYRAZONE SULFONE plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
116 mg × h/L	400 mg single, oral	SULFINPYRAZONE plasma	Homo sapiens
53 mg × h/L	400 mg 2 times / day multiple, oral	SULFINPYRAZONE plasma	Homo sapiens
13.4 mg × h/L	400 mg single, oral	SULFINPYRAZONE SULFONE plasma	Homo sapiens
9.2 mg × h/L	400 mg 2 times / day multiple, oral	SULFINPYRAZONE SULFONE plasma	Homo sapiens
79.6 μg × h/mL	200 mg single, oral	SULFINPYRAZONE plasma	Homo sapiens
191.9 μg × h/mL	400 mg single, oral	SULFINPYRAZONE plasma	Homo sapiens
5.7 μg × h/mL	200 mg single, oral	SULFINPYRAZONE SULFONE plasma	Homo sapiens
16.5 μg × h/mL	400 mg single, oral	SULFINPYRAZONE SULFONE plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
3.8 h	400 mg single, oral	SULFINPYRAZONE plasma	Homo sapiens
9.96 h	400 mg 2 times / day multiple, oral	SULFINPYRAZONE plasma	Homo sapiens
3.6 h	400 mg single, oral	SULFINPYRAZONE SULFONE plasma	Homo sapiens
3.3 h	400 mg 2 times / day multiple, oral	SULFINPYRAZONE SULFONE plasma	Homo sapiens
3.79 h	200 mg single, oral	SULFINPYRAZONE plasma	Homo sapiens
4.17 h	400 mg single, oral	SULFINPYRAZONE plasma	Homo sapiens
3.8 h	400 mg single, oral	SULFINPYRAZONE SULFONE plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
1000 mg single, oral Overdose	healthy, 24	Other AEs: Acute renal failure...
1000 mg multiple, oral Recommended	unhealthy	Other AEs: Acute renal failure...
400 mg 2 times / day multiple, oral Recommended	unhealthy	Disc. AE: Skin rash...

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AEs

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AE	Significance	Dose	Population
Acute renal failure		1000 mg single, oral Overdose	healthy, 24
Acute renal failure	low incidence	1000 mg multiple, oral Recommended	unhealthy
Skin rash	rare Disc. AE	400 mg 2 times / day multiple, oral Recommended	unhealthy

Showing 1 to 3 of 3 entries

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1,087 inhibitor 2,252	inhibitor 2,438

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 1,057 MRP4 290 MRP5 31 MRP1 116 MRP2 499 UGT1A1 246 UGT1A3 89 UGT1A4 98 UGT1A6 136 UGT1A7 23 UGT1A8 37 UGT1A9 148 UGT1A10 37 UGT2B7 197 UGT2B15 84		CYP2B6 669

Drug as perpetrator

Show entries

Target	Modality	Activity
CYP2B6 1,160	inducer 1,966	weak
MRP5 80	inhibitor 4,027	yes [IC50 103 uM]
UGT1A9 155	inhibitor 4,027	yes [IC50 11 uM]
UGT1A8 49	inhibitor 4,027	yes [IC50 158 uM]
UGT1A7 25	inhibitor 4,027	yes [IC50 16 uM]

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Sourcing

Sourcing

Show entries

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
eMolecules	544393	https://www.emolecules.com/cgi-bin/more?vid=544393
MolPort	MolPort-003-666-286	https://www.molport.com/shop/molecule-link/MolPort-003-666-286

Showing 1 to 4 of 4 entries

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PubMed

Show entries

Title	Date	PubMed
Are agents affecting platelet functions clinically useful?	1976 Dec	795299
Abnormalities of urinary sediment and renal failure following sulfinpyrazone therapy.	1976 Sep	962450
[Acute renal failure induced by sulfinpyrazone (author's transl)].	1981	7301034
Effects of sulfinpyrazone, aspirin and propranolol on the isoproterenol-induced myocardial necrosis.	1981 Jul	6272002
[Sulfinpyrazone-associated renal failure (author's transl)].	1982 Jul 9	7084072

Showing 1 to 5 of 10 entries

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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