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
Correlation of in vitro chemopreventive efficacy data from the human epidermal cell assay with animal efficacy data and clinical trial plasma levels.	2005-06-01	15786488
5-Lipoxygenase modulates colitis through the regulation of adhesion molecule expression and neutrophil migration.	2005-06	15821759
Leukotrienes: their role in the treatment of asthma and seasonal allergic rhinitis.	2005-03-30	15794321
Overexpression of 5-lipoxygenase and cyclooxygenase 2 in hamster and human oral cancer and chemopreventive effects of zileuton and celecoxib.	2005-03-01	15756036
The effects of a 5-lipoxygenase inhibitor on acute mountain sickness and urinary leukotriene e4 after ascent to high altitude.	2005-02	15705997
Asthma controller therapy during pregnancy.	2005-02	15695974
Zileuton, an oral 5-lipoxygenase inhibitor, directly reduces sebum production.	2005	15604543
Cetirizine and loratadine-based antihistamines with 5-lipoxygenase inhibitory activity.	2004-11-15	15482930
Anti-proliferative effects of lichen-derived lipoxygenase inhibitors on twelve human cancer cell lines of different tissue origin in vitro.	2004-11	15549672
Reduction of the multiple organ injury and dysfunction caused by endotoxemia in 5-lipoxygenase knockout mice and by the 5-lipoxygenase inhibitor zileuton.	2004-11	15328337
Modulation of pulmonary leukotriene B4 production by cyclooxygenase-2 inhibitors and lipopolysaccharide.	2004-10-15	15501964
Overexpression of 5-lipoxygenase in rat and human esophageal adenocarcinoma and inhibitory effects of zileuton and celecoxib on carcinogenesis.	2004-10-01	15475461
The improved survival of experimental animals fed with fish oil is suppressed by a leukotriene inhibitor.	2004-10	15379859
Aspirin-triggered, cyclooxygenase-2-dependent lipoxin synthesis modulates vascular tone.	2004-09-07	15326064
Reduction of renal ischemia-reperfusion injury in 5-lipoxygenase knockout mice and by the 5-lipoxygenase inhibitor zileuton.	2004-08	15266012
Involvement of mast cells in basal and neurotensin-induced intestinal absorption of taurocholate in rats.	2004-08	14693504
Effect of 5-lipoxygenase inhibition on events associated with inflammatory bowel disease in rats.	2004-07	15339030
Zileuton induces hemoglobin F synthesis in erythroid progenitors: role of the L-arginine-nitric oxide signaling pathway.	2004-05-15	14764535
Effect of 5-lipoxygenase on the development of pulmonary hypertension in rats.	2004-05	14726295
Evaluation of the utilization patterns of leukotriene modifiers in a large managed care health plan.	2004-03-23	15032560
Leukotriene modifier use and asthma severity: how is a new medication being used by adults with asthma?	2004-03-22	15037489
Suppression of leukotriene B4 generation by ex-vivo neutrophils isolated from asthma patients on dietary supplementation with gammalinolenic acid-containing borage oil: possible implication in asthma.	2004-03	15154607
In vitro metabolism of 2-acetylbenzothiophene: relevance to zileuton hepatotoxicity.	2004-02	14967000
Advances in therapy with antileukotriene drugs.	2004	15648777
Effect of zileuton in radicular pain induced by herniated nucleus pulposus in rats.	2004	15265319
Idiopathic pulmonary fibrosis: pathogenesis and therapeutic approaches.	2004	14969575
Generalized granuloma annulare in a patient with adult onset diabetes mellitus.	2003-12	14711148
Effects of imatinib mesylate (STI571, Glivec) on the pharmacokinetics of simvastatin, a cytochrome p450 3A4 substrate, in patients with chronic myeloid leukaemia.	2003-11-17	14612892
Inhibition of neutrophil leukotriene B4 production by a novel synthetic N-3 polyunsaturated fatty acid analogue, beta-oxa 21:3n-3.	2003-11-01	14568954
Mechanism-based inhibition of human liver microsomal cytochrome P450 1A2 by zileuton, a 5-lipoxygenase inhibitor.	2003-11	14570767
Deficiency of NADPH oxidase components p47phox and gp91phox caused granulomatous synovitis and increased connective tissue destruction in experimental arthritis models.	2003-10	14507659
Use of a low-density microarray for studying gene expression patterns induced by hepatotoxicants on primary cultures of rat hepatocytes.	2003-10	12883083
Leukotrienes mediate part of Ova-induced lung effects in mice via EGFR.	2003-10	12794006
Zileuton, a 5-lipoxygenase inhibitor, increases production of thromboxane A2 and platelet aggregation in patients with asthma.	2003-09	12949886
Tenofovir, COX inhibitors and zileuton during cancer immunotherapies: up-regulated TNF-alpha increases antigen driven lymphocyte proliferation.	2003-09	12943802
Zileuton reduces respiratory illness and lung inflammation, during respiratory syncytial virus infection, in mice.	2003-06-01	12751035
[Anti-leukotrienes in allergic diseases in children].	2003-06	14524289
The role of leukotriene inhibitors in patients with paranasal sinus disease.	2003-06	12923360
A new concept for acne therapy: a pilot study with zileuton, an oral 5-lipoxygenase inhibitor.	2003-05	12756111
Hyperalgesia induced by Asp49 and Lys49 phospholipases A2 from Bothrops asper snake venom: pharmacological mediation and molecular determinants.	2003-05	12727271
Leukotrienes mediate murine bronchopulmonary hyperreactivity, inflammation, and part of mucosal metaplasia and tissue injury induced by recombinant murine interleukin-13.	2003-04	12654629
Anti-leukotriene drugs in the prevention and treatment of hepatorenal syndrome.	2003-04	12628221
Toxicity of human monocytic THP-1 cells and microglia toward SH-SY5Y neuroblastoma cells is reduced by inhibitors of 5-lipoxygenase and its activating protein FLAP.	2003-03	12629151
Lipoxygenase and cyclooxygenase metabolism: new insights in treatment and chemoprevention of pancreatic cancer.	2003-01-07	12575899
Leukotrienes antagonists in the management of bronchial asthma.	2003	15529580
Recent advances in the management of asthma using leukotriene modifiers.	2003	14720013
Benefit-risk assessment of antileukotrienes in the management of asthma.	2003	12735786
Inhibition of 5-lipoxygenase activating protein decreases proteinuria in diabetic rats.	2002-09-17	12649539
Inhibition of 5-LO activating protein (FLAP) activity decreases proteinuria in streptozotocin (STZ)-induced diabetic rats.	2002	12664568
Effects of Celebrex and Zyflo on liver metastasis and lipidperoxidation in pancreatic cancer in Syrian hamsters.	2002	12553373

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