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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

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

Targets

Targets

Conditions

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

850003200000
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
PubMed

PubMed

TitleDatePubMed
Double-blinded, placebo-controlled, cross-over pilot study on the efficacy of zileuton for canine atopic dermatitis.
2001 Aug
Clinical and biochemical effects of zileuton in patients with the Sjögren-Larsson syndrome.
2001 Dec
ABT-761 (Abbott).
2001 Jan
Modulation of haem oxygenase-1 expression by nitric oxide and leukotrienes in zymosan-activated macrophages.
2001 Jul
Efficacy of antileukotriene agents in asthma management.
2001 Jun
Discovery of leukotrienes and development of antileukotriene agents.
2001 Jun
In vitro effects of E3040, a dual inhibitor of 5-lipoxygenase and thromboxane A(2) synthetase, on eicosanoid production.
2001 Jun 22
[Leukotriene modifiers].
2001 Oct
Acute effects of the cys-leukotriene-1 receptor antagonist, montelukast, on experimental colitis in rats.
2001 Oct 19
Leukotrienes in respiratory disease.
2001 Sep
Induction of hepatic microsomal drug-metabolizing enzymes by inhibitors of 5-lipoxygenase (5-LO): studies in rats and 5-LO knockout mice.
2001 Sep
Inhibition of 5-LO activating protein (FLAP) activity decreases proteinuria in streptozotocin (STZ)-induced diabetic rats.
2002
Effects of Celebrex and Zyflo on liver metastasis and lipidperoxidation in pancreatic cancer in Syrian hamsters.
2002
Effects of Celebrex and Zyflo on BOP-induced pancreatic cancer in Syrian hamsters.
2002
Chemoprevention by lipoxygenase and leukotriene pathway inhibitors of vinyl carbamate-induced lung tumors in mice.
2002 Aug 1
Hyperforin is a dual inhibitor of cyclooxygenase-1 and 5-lipoxygenase.
2002 Dec 15
[Anti-leukotriene drugs and Churg Strauss syndrome].
2002 Feb
Role of lung inflammatory mediators as a cause of exercise-induced arterial hypoxemia in young athletes.
2002 Jul
[New horizons in the treatment of atopic dermatitis].
2002 May-Jun
Mechanisms of idiosyncratic drug reactions: the case of felbamate.
2002 Nov 10
The effect of leukotriene-modifier drugs on aspirin-induced asthma and rhinitis reactions.
2002 Oct
Interaction between nitric oxide, reactive oxygen intermediates, and peroxynitrite in the regulation of 5-lipoxygenase metabolism.
2002 Oct 10
Mediators of adenosine- and ovalbumen-induced bronchoconstriction of sensitized guinea-pig isolated airways.
2002 Sep 6
Leukotrienes antagonists in the management of bronchial asthma.
2003
Anti-leukotriene drugs in the prevention and treatment of hepatorenal syndrome.
2003 Apr
Lipoxygenase and cyclooxygenase metabolism: new insights in treatment and chemoprevention of pancreatic cancer.
2003 Jan 7
[Anti-leukotrienes in allergic diseases in children].
2003 Jun
The role of leukotriene inhibitors in patients with paranasal sinus disease.
2003 Jun
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 Mar
Mechanism-based inhibition of human liver microsomal cytochrome P450 1A2 by zileuton, a 5-lipoxygenase inhibitor.
2003 Nov
Effects of imatinib mesylate (STI571, Glivec) on the pharmacokinetics of simvastatin, a cytochrome p450 3A4 substrate, in patients with chronic myeloid leukaemia.
2003 Nov 17
Deficiency of NADPH oxidase components p47phox and gp91phox caused granulomatous synovitis and increased connective tissue destruction in experimental arthritis models.
2003 Oct
Use of a low-density microarray for studying gene expression patterns induced by hepatotoxicants on primary cultures of rat hepatocytes.
2003 Oct
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
Tenofovir, COX inhibitors and zileuton during cancer immunotherapies: up-regulated TNF-alpha increases antigen driven lymphocyte proliferation.
2003 Sep
Involvement of mast cells in basal and neurotensin-induced intestinal absorption of taurocholate in rats.
2004 Aug
Advances in therapy with antileukotriene drugs.
2004 Autumn
In vitro metabolism of 2-acetylbenzothiophene: relevance to zileuton hepatotoxicity.
2004 Feb
Anti-proliferative effects of lichen-derived lipoxygenase inhibitors on twelve human cancer cell lines of different tissue origin in vitro.
2004 Nov
Cetirizine and loratadine-based antihistamines with 5-lipoxygenase inhibitory activity.
2004 Nov 15
The improved survival of experimental animals fed with fish oil is suppressed by a leukotriene inhibitor.
2004 Oct
Modulation of pulmonary leukotriene B4 production by cyclooxygenase-2 inhibitors and lipopolysaccharide.
2004 Oct 15
Zileuton, an oral 5-lipoxygenase inhibitor, directly reduces sebum production.
2005
The effects of a 5-lipoxygenase inhibitor on acute mountain sickness and urinary leukotriene e4 after ascent to high altitude.
2005 Feb
Asthma controller therapy during pregnancy.
2005 Feb
Leukotrienes: their role in the treatment of asthma and seasonal allergic rhinitis.
2005 Jan-Feb
5-Lipoxygenase modulates colitis through the regulation of adhesion molecule expression and neutrophil migration.
2005 Jun
Correlation of in vitro chemopreventive efficacy data from the human epidermal cell assay with animal efficacy data and clinical trial plasma levels.
2005 Jun 1
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
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).
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