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Details

Stereochemistry ACHIRAL
Molecular Formula C31H33N3O6S
Molecular Weight 575.6775
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ZAFIRLUKAST

SMILES

Cc1ccccc1S(=O)(=O)N=C(c2ccc(Cc3cn(C)c4ccc(cc34)N=C(O)OC5CCCC5)c(c2)OC)O

InChI

InChIKey=YEEZWCHGZNKEEK-UHFFFAOYSA-N
InChI=1S/C31H33N3O6S/c1-20-8-4-7-11-29(20)41(37,38)33-30(35)22-13-12-21(28(17-22)39-3)16-23-19-34(2)27-15-14-24(18-26(23)27)32-31(36)40-25-9-5-6-10-25/h4,7-8,11-15,17-19,25H,5-6,9-10,16H2,1-3H3,(H,32,36)(H,33,35)

HIDE SMILES / InChI

Description
Curator's Comment:: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020547s027lbl.pdf

Zafirlukast is an oral leukotriene receptor antagonist (LTRA) for the maintenance treatment of asthma, often used in conjunction with an inhaled steroid and/or long-acting bronchodilator. It is available as a tablet and is usually dosed twice daily. Zafirlukast is indicated for the prophylaxis and chronic treatment of asthma. Patients with asthma were found in one study to be 25-100 times more sensitive to the bronchoconstricting activity of inhaled LTD4 than nonasthmatic subjects. In vitro studies demonstrated that zafirlukast antagonized the contractile activity of three leukotrienes (LTC4, LTD4 and LTE4) in conducting airway smooth muscle from laboratory animals and humans. Zafirlukast prevented intradermal LTD4-induced increases in cutaneous vascular permeability and inhibited inhaled LTD4-induced influx of eosinophils into animal lungs. Zafirlukast is a selective and competitive receptor antagonist of leukotriene D4 and E4 (LTD4 and LTE4), components of slow-reacting substance of anaphylaxis (SRSA). Cysteinyl leukotriene production and receptor occupation have been correlated with the pathophysiology of asthma, including airway edema, smooth muscle constriction, and altered cellular activity associated with the inflammatory process, which contribute to the signs and symptoms of asthma. Zafirlukast is marketed by Astra Zeneca with the brand names Accolate, Accoleit, and Vanticon. It was the first LTRA to be marketed in the USA and is now approved in over 60 countries, including the UK, Japan, Taiwan, Italy, Spain, Canada, Brazil, China and Turkey.

CNS Activity

Curator's Comment:: Studies in rats using radiolabeled Zafirlukast indicate minimal distribution across the blood-brain barrier.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ACCOLATE

Approved Use

ACCOLATE is indicated for the prophylaxis and chronic treatment of asthma in adults and children 5 years of age and older.

Launch Date

843609600000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
352.7 ng/mL
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ZAFIRLUKAST plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1090.41 ng × h/mL
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ZAFIRLUKAST plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.3 h
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ZAFIRLUKAST plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources:
unhealthy, 12-76
Health Status: unhealthy
Age Group: 12-76
Sex: M+F
Sources:
Other AEs: Pharyngitis, Headache...
Other AEs:
Pharyngitis (24.7%)
Headache (13.8%)
Myalgia (3.7%)
Sinusitis (3.5%)
Flu syndrome (3.3%)
Cough increased (3.1%)
Rash (3.1%)
Rhinitis (3.1%)
Accidental injury (3.1%)
Nausea (3.1%)
Back pain (2.9%)
Hypertonia (2.9%)
Diarrhea (2.7%)
Exacerbation of asthma (2.7%)
Sources:
20 mg 2 times / day multiple, oral
Highest studied dose
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources:
unhealthy, 37
Health Status: unhealthy
Age Group: 37
Sex: M+F
Sources:
Other AEs: Headache, Gastritis...
Other AEs:
Headache (7%)
Gastritis (1%)
Pharyngitis (20%)
Rhinitis (7%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Headache 13.8%
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources:
unhealthy, 12-76
Health Status: unhealthy
Age Group: 12-76
Sex: M+F
Sources:
Diarrhea 2.7%
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources:
unhealthy, 12-76
Health Status: unhealthy
Age Group: 12-76
Sex: M+F
Sources:
Exacerbation of asthma 2.7%
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources:
unhealthy, 12-76
Health Status: unhealthy
Age Group: 12-76
Sex: M+F
Sources:
Back pain 2.9%
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources:
unhealthy, 12-76
Health Status: unhealthy
Age Group: 12-76
Sex: M+F
Sources:
Hypertonia 2.9%
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources:
unhealthy, 12-76
Health Status: unhealthy
Age Group: 12-76
Sex: M+F
Sources:
Pharyngitis 24.7%
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources:
unhealthy, 12-76
Health Status: unhealthy
Age Group: 12-76
Sex: M+F
Sources:
Accidental injury 3.1%
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources:
unhealthy, 12-76
Health Status: unhealthy
Age Group: 12-76
Sex: M+F
Sources:
Cough increased 3.1%
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources:
unhealthy, 12-76
Health Status: unhealthy
Age Group: 12-76
Sex: M+F
Sources:
Nausea 3.1%
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources:
unhealthy, 12-76
Health Status: unhealthy
Age Group: 12-76
Sex: M+F
Sources:
Rash 3.1%
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources:
unhealthy, 12-76
Health Status: unhealthy
Age Group: 12-76
Sex: M+F
Sources:
Rhinitis 3.1%
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources:
unhealthy, 12-76
Health Status: unhealthy
Age Group: 12-76
Sex: M+F
Sources:
Flu syndrome 3.3%
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources:
unhealthy, 12-76
Health Status: unhealthy
Age Group: 12-76
Sex: M+F
Sources:
Sinusitis 3.5%
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources:
unhealthy, 12-76
Health Status: unhealthy
Age Group: 12-76
Sex: M+F
Sources:
Myalgia 3.7%
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources:
unhealthy, 12-76
Health Status: unhealthy
Age Group: 12-76
Sex: M+F
Sources:
Gastritis 1%
20 mg 2 times / day multiple, oral
Highest studied dose
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources:
unhealthy, 37
Health Status: unhealthy
Age Group: 37
Sex: M+F
Sources:
Pharyngitis 20%
20 mg 2 times / day multiple, oral
Highest studied dose
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources:
unhealthy, 37
Health Status: unhealthy
Age Group: 37
Sex: M+F
Sources:
Headache 7%
20 mg 2 times / day multiple, oral
Highest studied dose
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources:
unhealthy, 37
Health Status: unhealthy
Age Group: 37
Sex: M+F
Sources:
Rhinitis 7%
20 mg 2 times / day multiple, oral
Highest studied dose
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources:
unhealthy, 37
Health Status: unhealthy
Age Group: 37
Sex: M+F
Sources:
PubMed

PubMed

TitleDatePubMed
Comparison of the bronchodilating effect of salmeterol and zafirlukast in combination with that of their use as single treatments in asthma and chronic obstructive pulmonary disease.
2001
Addition of anti-leukotriene agents to inhaled corticosteroids for chronic asthma.
2001
Cost-efficacy analysis of fluticasone propionate versus zafirlukast in patients with persistent asthma.
2001
Comparative efficacy of inhaled corticosteroids and antileukotriene drugs in asthma.
2001
A comparison of short-term treatment with inhaled fluticasone propionate and zafirlukast for patients with persistent asthma.
2001 Aug 15
Fluticasone propionate compared with zafirlukast in controlling persistent asthma: a randomized double-blind, placebo-controlled trial.
2001 Jul
Comparison of inhaled salmeterol and oral zafirlukast in asthmatic patients using concomitant inhaled corticosteroids.
2001 Jul 5
[The relationship between eosinophils, activated T lymphocyte, leukotreine and the exercise-induced asthma].
2001 Jun
Efficacy of antileukotriene agents in asthma management.
2001 Jun
Discovery of leukotrienes and development of antileukotriene agents.
2001 Jun
Role of cysteinyl leukotrienes in nociceptive and inflammatory conditions in experimental animals.
2001 Jun 29
Synergistic antiallergic activity of combined histamine H1- and cysteinyl leukotriene1-receptor blockade in human bronchus.
2001 May 11
Molecular cloning and functional characterization of murine cysteinyl-leukotriene 1 (CysLT(1)) receptors.
2001 Nov 1
The effect of low-dose inhaled fluticasone propionate on exhaled nitric oxide in asthmatic patients and comparison with oral zafirlukast.
2001 Oct
Asthma treatment with inhaled corticosteroids versus antileukotrienes: what exhaled nitric oxide studies do and do not tell us.
2001 Oct
Acute hepatocellular injury associated with zafirlukast.
2001 Oct
Zafirlukast-related hepatitis: report of a further case.
2001 Oct
[Leukotriene modifiers].
2001 Oct
Leukotriene receptor antagonists in the treatment of allergic rhinitis.
2001 Oct
Severe liver injury.
2001 Oct 2
Chronic asthma.
2001 Oct 27
An open study to evaluate the safety and efficacy of zafirlukast ("Accolate") in patients with mild to moderate asthma in Ibadan, Nigeria.
2001 Oct-Dec
Effects of zafirlukast upon clinical, physiologic, and inflammatory responses to natural cat allergen exposure.
2001 Sep
Fulminant eosinophilic endomyocarditis in an asthmatic patient treated with pranlukast after corticosteroid withdrawal.
2001 Sep
Leukotriene receptor antagonists in the treatment of asthma: an update.
2002
Pharmacokinetic profile of zafirlukast.
2002
Loss of response to treatment with leukotriene receptor antagonists but not inhaled corticosteroids in patients over 50 years of age.
2002 Apr
[Zafirlukast (Accolate): a review of its pharmacological and clinical profile].
2002 Apr
Pharmacogenetics of asthma.
2002 Apr 1
Vasculitis induced by zafirlukast therapy.
2002 Aug
Chemoprevention by lipoxygenase and leukotriene pathway inhibitors of vinyl carbamate-induced lung tumors in mice.
2002 Aug 1
Participation of chemical mediators other than histamine in nasal allergy signs: a study using mice lacking histamine H(1) receptors.
2002 Aug 9
Pharmacoeconomic studies of asthma controller drugs: marketing gimmick or icing on the cake?
2002 Feb
Receptor preferences of cysteinyl-leukotrienes in the guinea pig lung parenchyma.
2002 Feb 1
[Churg-Strauss syndrome after treatment with Singulair (montelukast)].
2002 Feb 20
[Study on relationship between leukotrienes and exercise-induced asthma].
2002 Jan 10
Effects of adding either a leukotriene receptor antagonist or low-dose theophylline to a low or medium dose of inhaled corticosteroid in patients with persistent asthma.
2002 Jul
Efficacy and safety of low-dose fluticasone propionate compared with zafirlukast in patients with persistent asthma.
2002 Jul
Churg-Strauss syndrome in a case of asthma.
2002 Jul
5-Lipoxygenase polymorphism and in-vivo response to leukotriene receptor antagonists.
2002 Jun
Antitussive effect of the leukotriene receptor antagonist zafirlukast in subjects with cough-variant asthma.
2002 Jun
Pulmonary function changes and immunomodulation of cytokine expression by zafirlukast after sensitization and allergen challenge in brown Norway rats.
2002 Jun
[Zafirlukast in treatment of nasal polyps in patients with aspirin intolerant bronchial asthma--preliminary report].
2002 Mar
Prevalence of serious eosinophilia and incidence of Churg-Strauss syndrome in a cohort of asthma patients.
2002 Mar
Treatment of canine atopic dermatitis with zafirlukast, a leukotriene-receptor antagonist: a single-blinded, placebo-controlled study.
2002 Mar
Inhaled fluticasone and zafirlukast in persistent asthma.
2002 Mar
[Aspirin induced asthma, urinary leukotriene E4 and zafirlukast].
2002 Mar-Apr
Comparison of second controller medications in addition to inhaled corticosteroid in patients with moderate asthma.
2002 May
Exercise-induced asthma: is there still a case for histamine?
2002 May
[New horizons in the treatment of atopic dermatitis].
2002 May-Jun
Patents

Sample Use Guides

Should be taken at least 1 hour before or 2 hours after meals. Adults and Children 12 years of age and older
Route of Administration: Oral
In Vitro Use Guide
Zafirlukast significantly inhibited 10 uM LTD4-evoked 35SO4 output in a concentration-dependent fashion, with maximal inhibition of 78% at 10 uM zafirlukast, and IC50 value of 0.6 uM.
Name Type Language
ZAFIRLUKAST
INN   JAN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
ZAFIRLUKAST [MART.]
Common Name English
CYCLOPENTYL 3-(2-METHOXY-4-((O-TOLYLSULFONYL)CARBAMOYL)BENZYL)-1-METHYLINDOLE-5-CARBAMATE
Common Name English
ZAFIRLUKAST [WHO-DD]
Common Name English
ZAFIRLUKAST [USAN]
Common Name English
ICI-204,219
Common Name English
ICI 204,219
Code English
ICI-204219
Code English
ZAFIRLUKAST [MI]
Common Name English
ACCOLATE
Brand Name English
ZAFIRLUKAST [VANDF]
Common Name English
ZAFIRLUKAST [ORANGE BOOK]
Common Name English
ZAFIRLUKAST [INN]
Common Name English
ZAFIRLUKAST [JAN]
Common Name English
CARBAMIC ACID, (3-((2-METHOXY-4-(((2-METHYLPHENYL)SULFONYL)AMINO)CARBONYL)PHENYL)METHYL)-1-METHYL-1H-INDOL-5-YL)-, CYCLOPENTYL ESTER
Common Name English
Classification Tree Code System Code
NDF-RT N0000175777
Created by admin on Fri Jun 25 23:37:48 UTC 2021 , Edited by admin on Fri Jun 25 23:37:48 UTC 2021
NDF-RT N0000000083
Created by admin on Fri Jun 25 23:37:48 UTC 2021 , Edited by admin on Fri Jun 25 23:37:48 UTC 2021
NCI_THESAURUS C29712
Created by admin on Fri Jun 25 23:37:48 UTC 2021 , Edited by admin on Fri Jun 25 23:37:48 UTC 2021
LIVERTOX 1043
Created by admin on Fri Jun 25 23:37:48 UTC 2021 , Edited by admin on Fri Jun 25 23:37:48 UTC 2021
WHO-ATC R03DC01
Created by admin on Fri Jun 25 23:37:48 UTC 2021 , Edited by admin on Fri Jun 25 23:37:48 UTC 2021
WHO-VATC QR03DC01
Created by admin on Fri Jun 25 23:37:48 UTC 2021 , Edited by admin on Fri Jun 25 23:37:48 UTC 2021
Code System Code Type Description
CAS
107753-78-6
Created by admin on Fri Jun 25 23:37:48 UTC 2021 , Edited by admin on Fri Jun 25 23:37:48 UTC 2021
PRIMARY
MERCK INDEX
M11576
Created by admin on Fri Jun 25 23:37:48 UTC 2021 , Edited by admin on Fri Jun 25 23:37:48 UTC 2021
PRIMARY Merck Index
INN
7244
Created by admin on Fri Jun 25 23:37:48 UTC 2021 , Edited by admin on Fri Jun 25 23:37:48 UTC 2021
PRIMARY
FDA UNII
XZ629S5L50
Created by admin on Fri Jun 25 23:37:48 UTC 2021 , Edited by admin on Fri Jun 25 23:37:48 UTC 2021
PRIMARY
EVMPD
SUB00128MIG
Created by admin on Fri Jun 25 23:37:48 UTC 2021 , Edited by admin on Fri Jun 25 23:37:48 UTC 2021
PRIMARY
ChEMBL
CHEMBL603
Created by admin on Fri Jun 25 23:37:48 UTC 2021 , Edited by admin on Fri Jun 25 23:37:48 UTC 2021
PRIMARY
NCI_THESAURUS
C47785
Created by admin on Fri Jun 25 23:37:48 UTC 2021 , Edited by admin on Fri Jun 25 23:37:48 UTC 2021
PRIMARY
PUBCHEM
5717
Created by admin on Fri Jun 25 23:37:48 UTC 2021 , Edited by admin on Fri Jun 25 23:37:48 UTC 2021
PRIMARY
IUPHAR
3322
Created by admin on Fri Jun 25 23:37:48 UTC 2021 , Edited by admin on Fri Jun 25 23:37:48 UTC 2021
PRIMARY
DRUG BANK
DB00549
Created by admin on Fri Jun 25 23:37:48 UTC 2021 , Edited by admin on Fri Jun 25 23:37:48 UTC 2021
PRIMARY
EPA CompTox
107753-78-6
Created by admin on Fri Jun 25 23:37:48 UTC 2021 , Edited by admin on Fri Jun 25 23:37:48 UTC 2021
PRIMARY
LACTMED
Zafirlukast
Created by admin on Fri Jun 25 23:37:48 UTC 2021 , Edited by admin on Fri Jun 25 23:37:48 UTC 2021
PRIMARY
WIKIPEDIA
ZAFIRLUKAST
Created by admin on Fri Jun 25 23:37:48 UTC 2021 , Edited by admin on Fri Jun 25 23:37:48 UTC 2021
PRIMARY
DRUG CENTRAL
2855
Created by admin on Fri Jun 25 23:37:48 UTC 2021 , Edited by admin on Fri Jun 25 23:37:48 UTC 2021
PRIMARY
MESH
C062735
Created by admin on Fri Jun 25 23:37:48 UTC 2021 , Edited by admin on Fri Jun 25 23:37:48 UTC 2021
PRIMARY
RXCUI
114970
Created by admin on Fri Jun 25 23:37:48 UTC 2021 , Edited by admin on Fri Jun 25 23:37:48 UTC 2021
PRIMARY RxNorm
NDF-RT
N0000185504
Created by admin on Fri Jun 25 23:37:48 UTC 2021 , Edited by admin on Fri Jun 25 23:37:48 UTC 2021
PRIMARY Cytochrome P450 2C9 Inhibitors [MoA]