ZILEUTON

Details

Stereochemistry	RACEMIC
Molecular Formula	C11H12N2O2S
Molecular Weight	236.29
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(N(O)C(N)=O)C1=CC2=C(S1)C=CC=C2

InChI

InChIKey=MWLSOWXNZPKENC-UHFFFAOYSA-N

InChI=1S/C11H12N2O2S/c1-7(13(15)11(12)14)10-6-8-4-2-3-5-9(8)16-10/h2-7,15H,1H3,(H2,12,14)

HIDE SMILES / InChI

Molecular Formula	C11H12N2O2S
Molecular Weight	236.29
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020471s017lbl.pdf
Curator's Comment: Description was created based on several sources, including

Zileuton is an asthma drug that differs chemically and pharmacologically from other antiasthmatic agents. It blocks leukotriene synthesis by inhibiting 5-lipoxygenase, an enzyme of the eicosanoid synthesis pathway. Current data indicates that asthma is a chronic inflammatory disorder of the airways involving the production and activity of several endogenous inflammatory mediators, including leukotrienes. Sulfido-peptide leukotrienes (LTC4, LTD4, LTE4, also known as the slow-releasing substances of anaphylaxis) and LTB4, a chemoattractant for neutrophils and eosinophils, are derived from the initial unstable product of arachidonic acid metabolism, leukotriene A4 (LTA4), and can be measured in a number of biological fluids including bronchoalveolar lavage fluid (BALF) from asthmatic patients. In humans, pretreatment with zileuton attenuated bronchoconstriction caused by cold air challenge in patients with asthma. Zileuton is a specific inhibitor of 5-lipoxygenase and thus inhibits leukotriene (LTB4, LTC4, LTD4, and LTE4) formation. Both the R(+) and S(-) enantiomers are pharmacologically active as 5-lipoxygenase inhibitors in in vitro systems. Leukotrienes are substances that induce numerous biological effects including augmentation of neutrophil and eosinophil migration, neutrophil and monocyte aggregation, leukocyte adhesion, increased capillary permeability, and smooth muscle contraction. These effects contribute to inflammation, edema, mucus secretion, and bronchoconstriction in the airways of asthmatic patients. Zileuton is marketed under the trade name ZYFLO.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Arachidonate 5-lipoxygenase 52 Target ID: CHEMBL215 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020471s017lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/27717142	Inhibitor 8504		0.3 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Asthma 244 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020471s017lbl.pdf	Primary		Approved 8583	ZYFLO Approved Use ZYFLO is indicated for the prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older. Launch Date 1996

C_max

Value	Dose	Analyte	Population
5.15 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FED
4.25 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
5.69 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FED
4.82 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
7.55 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg 4 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FED
7.13 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg 4 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
7.63 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg 4 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FED
7.47 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg 4 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
4.98 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020471s017lbl.pdf	600 mg 4 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	ZILEUTON plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
21.28 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FED
19.1 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
26.34 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FED
23.23 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
29.09 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg 4 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FED
28.03 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg 4 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
30.18 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg 4 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FED
26.51 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg 4 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
19.2 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020471s017lbl.pdf	600 mg 4 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	ZILEUTON plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
1.85 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FED
2.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
2.12 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FED
2.34 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
1.77 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg 4 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FED
2.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg 4 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
2.12 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg 4 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FED
2.21 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg 4 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

F_unbound

Value	Dose	Analyte	Population
7.08% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FED
6.98% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
7.23% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FED
6.7% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
7.04% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg 4 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FED
7.01% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg 4 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
7.32% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg 4 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FED
6.73% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8620670/	600 mg 4 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ZILEUTON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
7% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020471s017lbl.pdf	600 mg 4 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	ZILEUTON plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:10112	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:10112
ChemicalBook	CB1344903	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1344903
eMolecules	876280	https://www.emolecules.com/cgi-bin/more?vid=876280
MolPort	MolPort-003-850-877	https://www.molport.com/shop/molecule-link/MolPort-003-850-877
Selleck Chemicals	Zileuton	http://www.selleckchem.com/products/Zileuton.html

PubMed

Title	Date	PubMed
Inhibition by troglitazone of the antigen-induced production of leukotrienes in immunoglobulin E-sensitized RBL-2H3 cells.	2000 Jan	10694244
Role of petasin in the potential anti-inflammatory activity of a plant extract of petasites hybridus.	2001 Apr 15	11286996
Zileuton and atopic dermatitis.	2001 Aug	11527251
Involvement of leukotriene B(4) in substance P-induced itch-associated response in mice.	2001 Dec	11886531
Role of the IgE-mediated system in eosinophil recruitment triggered by two consecutive cycles of sensitisation and challenge in rats.	2001 Dec	11815740
Clinical and biochemical effects of zileuton in patients with the Sjögren-Larsson syndrome.	2001 Dec	11795678
Leukotriene inhibitors and non-steroidal therapies in the treatment of asthma.	2001 Jan	11336568
Efficacy of antileukotriene agents in asthma management.	2001 Jun	11426917
Discovery of leukotrienes and development of antileukotriene agents.	2001 Jun	11426915
The role of antileukotrienes in the treatment of asthma.	2001 Jun	11426914
Safety of antileukotriene agents in asthma management.	2001 Jun	11426912
Antileukotrienes in asthma: present situation.	2001 Mar	11336598
Leukotrienes play protective roles early during experimental VSV encephalitis.	2001 Nov 1	11694324
Acute effects of the cys-leukotriene-1 receptor antagonist, montelukast, on experimental colitis in rats.	2001 Oct 19	11698051
Leukotrienes in respiratory disease.	2001 Sep	12052325
Effects of Celebrex and Zyflo on BOP-induced pancreatic cancer in Syrian hamsters.	2002	12120008
Pharmacogenetics, pharmacogenomics and airway disease.	2002	11806845
Treatment of disseminated granuloma annulare with a 5-lipoxygenase inhibitor and vitamin E.	2002 Apr	11966702
Monocyte chemoattractant protein-1 and 5-lipoxygenase products recruit leukocytes in response to platelet-activating factor-like lipids in oxidized low-density lipoprotein.	2002 Apr 15	11937571
Chemoprevention by lipoxygenase and leukotriene pathway inhibitors of vinyl carbamate-induced lung tumors in mice.	2002 Aug 1	12154018
[Anti-leukotriene drugs and Churg Strauss syndrome].	2002 Feb	12107974
Pharmacological characterization of SC-57461A (3-[methyl[3-[4-(phenylmethyl)phenoxy]propyl]amino]propanoic acid HCl), a potent and selective inhibitor of leukotriene A(4) hydrolase II: in vivo studies.	2002 Feb	11805220
Role of lung inflammatory mediators as a cause of exercise-induced arterial hypoxemia in young athletes.	2002 Jul	12070194
Thioglycollate peritonitis in mice lacking C5, 5-lipoxygenase, or p47(phox): complement, leukotrienes, and reactive oxidants in acute inflammation.	2002 Mar	11867678
Role of Ca(2+)-independent phospholipase A(2) and cyclooxygenase/lipoxygenase pathways in the nitric oxide production by murine macrophages stimulated by lipopolysaccharides.	2002 May	12009843
[New horizons in the treatment of atopic dermatitis].	2002 May-Jun	11988144
The effect of leukotriene-modifier drugs on aspirin-induced asthma and rhinitis reactions.	2002 Oct	12372130
Interaction between nitric oxide, reactive oxygen intermediates, and peroxynitrite in the regulation of 5-lipoxygenase metabolism.	2002 Oct 10	12385890
Mediators of adenosine- and ovalbumen-induced bronchoconstriction of sensitized guinea-pig isolated airways.	2002 Sep 6	12223233
Leukotrienes, IL-13, and chemokines cooperate to induce BHR and mucus in allergic mouse lungs.	2003 Feb	12388339
The role of leukotriene inhibitors in patients with paranasal sinus disease.	2003 Jun	12923360
Mechanism-based inhibition of human liver microsomal cytochrome P450 1A2 by zileuton, a 5-lipoxygenase inhibitor.	2003 Nov	14570767
Inhibition of neutrophil leukotriene B4 production by a novel synthetic N-3 polyunsaturated fatty acid analogue, beta-oxa 21:3n-3.	2003 Nov 1	14568954
Deficiency of NADPH oxidase components p47phox and gp91phox caused granulomatous synovitis and increased connective tissue destruction in experimental arthritis models.	2003 Oct	14507659
Zileuton, a 5-lipoxygenase inhibitor, increases production of thromboxane A2 and platelet aggregation in patients with asthma.	2003 Sep	12949886
Tenofovir, COX inhibitors and zileuton during cancer immunotherapies: up-regulated TNF-alpha increases antigen driven lymphocyte proliferation.	2003 Sep	12943802
Anti-proliferative effects of lichen-derived lipoxygenase inhibitors on twelve human cancer cell lines of different tissue origin in vitro.	2004 Nov	15549672
Zileuton, an oral 5-lipoxygenase inhibitor, directly reduces sebum production.	2005	15604543
Leukotrienes: their role in the treatment of asthma and seasonal allergic rhinitis.	2005 Jan-Feb	15794321
5-Lipoxygenase modulates colitis through the regulation of adhesion molecule expression and neutrophil migration.	2005 Jun	15821759

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dosage of ZYFLO (Zileuton) for the symptomatic treatment of patien ts with asthma is one 600-mg tablet four times a day for a total daily dose of 2400 mg. For ease of administration, ZYFLO may be taken with meals and at bedtime.

Route of Administration: Oral

In Vitro Use Guide

Zileuton (5 uM) inhibited LTB4 production by 99% in purified human neutrophils in the presence of fatty acid saturated albumin (fraction V).

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:12:06 GMT 2025` Edited by `admin` on `Mon Mar 31 18:12:06 GMT 2025`
Record UNII	V1L22WVE2S
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ZYFLO

Preferred Name

English

ZILEUTON

Official Name

English

NSC-730712

Code

English

(±)-1-(1-BENZO(B)THIEN-2-YLETHYL)-1-HYDROXYUREA

Systematic Name

English

UREA, N-(1-BENZO(B)THIEN-2-YLETHYL)-N-HYDROXY-, (±)-

Systematic Name

English

ZILEUTON [USAN]

Common Name

English

NSC-759277

Code

English

ZILEUTON [USP-RS]

Common Name

English

zileuton [INN]

Common Name

English

ZILEUTON [MI]

Common Name

English

A-64077

Code

English

ZILEUTON [USP MONOGRAPH]

Common Name

English

ABBOTT-64077

Code

English

ZILEUTON [ORANGE BOOK]

Common Name

English

ZILEUTON [MART.]

Common Name

English

Zileuton [WHO-DD]

Common Name

English

ZILEUTON [VANDF]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000008683