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Details

Stereochemistry RACEMIC
Molecular Formula C11H12N2O2S
Molecular Weight 236.2917
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ZILEUTON

SMILES

CC(c1cc2ccccc2s1)N(C(=N)O)O

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 236.2917
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Description
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.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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

8.5000323E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
4.98 μg/mL
600 mg 4 times / day multiple, oral
dose: 600 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ZILEUTON unknown
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
19.2 μg × h/mL
600 mg 4 times / day multiple, oral
dose: 600 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ZILEUTON unknown
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
600 mg 4 times / day multiple, oral
Studied dose
Dose: 600 mg, 4 times / day
Route: oral
Route: multiple
Dose: 600 mg, 4 times / day
Sources: Page: p.846
unhealthy, ADULT
n = 2458
Health Status: unhealthy
Condition: chronic asthma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 2458
Sources: Page: p.846
Disc. AE: Dyspepsia...
Other AEs: Nausea, ALT increased...
AEs leading to
discontinuation/dose reduction:
Dyspepsia (1.6%)
Other AEs:
Nausea (2.4%)
ALT increased (2.7%)
Asthma (3.7%)
Sources: Page: p.846
AEs

AEs

AESignificanceDosePopulation
Dyspepsia 1.6%
Disc. AE
600 mg 4 times / day multiple, oral
Studied dose
Dose: 600 mg, 4 times / day
Route: oral
Route: multiple
Dose: 600 mg, 4 times / day
Sources: Page: p.846
unhealthy, ADULT
n = 2458
Health Status: unhealthy
Condition: chronic asthma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 2458
Sources: Page: p.846
Nausea 2.4%
600 mg 4 times / day multiple, oral
Studied dose
Dose: 600 mg, 4 times / day
Route: oral
Route: multiple
Dose: 600 mg, 4 times / day
Sources: Page: p.846
unhealthy, ADULT
n = 2458
Health Status: unhealthy
Condition: chronic asthma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 2458
Sources: Page: p.846
ALT increased 2.7%
600 mg 4 times / day multiple, oral
Studied dose
Dose: 600 mg, 4 times / day
Route: oral
Route: multiple
Dose: 600 mg, 4 times / day
Sources: Page: p.846
unhealthy, ADULT
n = 2458
Health Status: unhealthy
Condition: chronic asthma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 2458
Sources: Page: p.846
Asthma 3.7%
600 mg 4 times / day multiple, oral
Studied dose
Dose: 600 mg, 4 times / day
Route: oral
Route: multiple
Dose: 600 mg, 4 times / day
Sources: Page: p.846
unhealthy, ADULT
n = 2458
Health Status: unhealthy
Condition: chronic asthma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 2458
Sources: Page: p.846
PubMed

PubMed

TitleDatePubMed
Effects of Celebrex and Zyflo on liver metastasis and lipidperoxidation in pancreatic cancer in Syrian hamsters.
2002
Hyperforin is a dual inhibitor of cyclooxygenase-1 and 5-lipoxygenase.
2002 Dec 15
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
Leukotrienes mediate murine bronchopulmonary hyperreactivity, inflammation, and part of mucosal metaplasia and tissue injury induced by recombinant murine interleukin-13.
2003 Apr
[Anti-leukotrienes in allergic diseases in children].
2003 Jun
Leukotrienes mediate part of Ova-induced lung effects in mice via EGFR.
2003 Oct
Zileuton, a 5-lipoxygenase inhibitor, increases production of thromboxane A2 and platelet aggregation in patients with asthma.
2003 Sep
Anti-proliferative effects of lichen-derived lipoxygenase inhibitors on twelve human cancer cell lines of different tissue origin in vitro.
2004 Nov
The effects of a 5-lipoxygenase inhibitor on acute mountain sickness and urinary leukotriene e4 after ascent to high altitude.
2005 Feb
Leukotrienes: their role in the treatment of asthma and seasonal allergic rhinitis.
2005 Jan-Feb
Overexpression of 5-lipoxygenase and cyclooxygenase 2 in hamster and human oral cancer and chemopreventive effects of zileuton and celecoxib.
2005 Mar 1
Patents

Sample Use Guides

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
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 Fri Jun 25 20:33:10 UTC 2021
Edited
by admin
on Fri Jun 25 20:33:10 UTC 2021
Record UNII
V1L22WVE2S
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ZILEUTON
INN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
INN   USAN  
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
ZYFLO
Brand Name English
A-64077
Code English
ZILEUTON [USP MONOGRAPH]
Common Name English
ABBOTT-64077
Code English
ZILEUTON [WHO-DD]
Common Name English
ZILEUTON [ORANGE BOOK]
Common Name English
ZILEUTON [MART.]
Common Name English
ZILEUTON [VANDF]
Common Name English
Classification Tree Code System Code
NDF-RT N0000008683
Created by admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
NDF-RT N0000175956
Created by admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
LIVERTOX 1048
Created by admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
NCI_THESAURUS C1322
Created by admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
NDF-RT N0000175955
Created by admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
NDF-RT N0000008683
Created by admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
Code System Code Type Description
DRUG BANK
DB00744
Created by admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
PRIMARY
ChEMBL
CHEMBL93
Created by admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
PRIMARY
CAS
111406-87-2
Created by admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
PRIMARY
INN
6595
Created by admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
PRIMARY
NCI_THESAURUS
C26667
Created by admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
PRIMARY
LACTMED
Zileuton
Created by admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
PRIMARY
MESH
C063449
Created by admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
PRIMARY
USP_CATALOG
1724656
Created by admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
PRIMARY USP-RS
WIKIPEDIA
ZILEUTON
Created by admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
PRIMARY
PUBCHEM
60490
Created by admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
PRIMARY
EVMPD
SUB00157MIG
Created by admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
PRIMARY
EPA CompTox
111406-87-2
Created by admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
PRIMARY
RXCUI
40575
Created by admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
PRIMARY RxNorm
FDA UNII
V1L22WVE2S
Created by admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
PRIMARY
MERCK INDEX
M11593
Created by admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
PRIMARY Merck Index
IUPHAR
5297
Created by admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
PRIMARY
DRUG CENTRAL
2862
Created by admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
PRIMARY
Related Record Type Details
EXCRETED UNCHANGED
FECAL; URINE
METABOLIC ENZYME -> SUBSTRATE
ENANTIOMER -> RACEMATE
ENANTIOMER -> RACEMATE
METABOLIC ENZYME -> SUBSTRATE
BINDER->LIGAND
BINDING
TARGET -> INHIBITOR
BINDER->LIGAND
BINDING
METABOLIC ENZYME -> SUBSTRATE
Related Record Type Details
METABOLITE -> PARENT
IN-VITRO
METABOLITE -> PARENT
METABOLITE -> PARENT
IN-VITRO
METABOLITE -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Route of Elimination PHARMACOKINETIC
Tmax PHARMACOKINETIC ORAL ADMINISTRATION

Volume of Distribution PHARMACOKINETIC
Tmax PHARMACOKINETIC ORAL ADMINISTRATION

FED CONDITION

Route of Elimination PHARMACOKINETIC