CAS 107753-78-6|cyclopentyl N-[3-({2-methoxy-4-[(2-methylbenzenesulfonyl)carbamoyl]phenyl}methyl)-1-methylindol-5-yl]carbamate|Zafirlukast|cyclopentyl N-[3-({2-methoxy-4-[(2-methylbenzenesulfonyl)ca...

General Information

Structure

Molecular Formula

C₃₁H₃₃N₃O₆S

Molecular Mass

575.67522

Exact Mass

575.20900679

Charge

InChI

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)

InChIKey

YEEZWCHGZNKEEK-UHFFFAOYSA-N

Canonic Smiles

COc1cc(ccc1Cc1cn(c2c1cc(cc2)NC(=O)OC1CCCC1)C)C(=O)NS(=O)(=O)c1ccccc1C

Isomeric Smiles

S(=O)(=O)(NC(=O)c1cc(OC)c(Cc2c3c(n(c2)C)ccc(NC(=O)OC2CCCC2)c3)cc1)c1c(cccc1)C

Calculated Properties

JChem

LogD (pH = 7.4)

5.46

LogD (pH = 5.5)

5.62

Log P

6.40

Rotatable Bonds

H Donor

H Acceptors

Lipinski's Rule of Five

false

Acid pKa

4.29

Polar Surface Area

115.73

Polarizability

61.93

Molar Refractivity

158.58

LOG S

-6.09

Data Source

Names and Identifiers

IUPAC Traditional name

cyclopentyl N-[3-({2-methoxy-4-[(2-methylbenzenesulfonyl)carbamoyl]phenyl}methyl)-1-methylindol-5-yl]carbamate zafirlukast cyclopentyl N-[3-({2-methoxy-4-[(2-methylbenzenesulfonyl)carbamoyl]phenyl}methyl)-1-methyl-1H-indol-5-yl]carbamate

Synonyms

ZafirlukastzafirlukastZafirlukastN-[3-[[2-Methoxy-4-[[[(2-methylphenyl)sulfonyl]amino]carbonyl]phenyl]methyl]-1-methyl-1H-indol-5-yl]carbamic acid cyclopentyl esterAccolate[3-[[2-Methoxy-4-[[[(2-methylphenyl)sulfonyl]amino]carbonyl]phenyl]methyl]-1-methyl-1H-indol-5-yl]carbamic Acid Cyclopentyl EsterVanticonICI-2204219cyclopentyl 3-(2-methoxy-4-((o-tolylsulfonyl)carbamoyl)benzyl)-1-methylindole-5-carbamatezafirlukast4-(5-cyclopentyloxycarbonylamino-1-methyl-1H-indol-3-ylmethyl)-3-methoxy-N-o-tolylsulfonylbenzamide

IUPAC name

cyclopentyl N-[3-({2-methoxy-4-[(2-methylbenzenesulfonyl)carbamoyl]phenyl}methyl)-1-methyl-1H-indol-5-yl]carbamate

Brand Name

Accolate

API Name

Zafirlukast

International Nonproprietary Name (INN)

zafirlukast

Names and Identifiers

Registration numbers

Properties

Pharmacology Properties

Target

Respiratory Diseases

Mechanism of Action

Potent leukotriene D4 receptor antagonist (LTRA)

Safety Information

Product Information

Salt Data

Free Base

Purity

≥98% (HPLC)

Empirical Formula (Hill Notation)

C31H33N3O6S

Certificate of Analysis

Download link

Application(s)

Antiasthmatic agent

Properties

Related Proteins

PDB Bank

6RZ5

Related Proteins

Molecular Spectra

No Data Available

Click here to submit data

Molecule Details

DrugBank

DB00549

Drug Groups

approved; investigational

Description

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. Another leukotriene receptor antagonist is montelukast (Singulair), which is usually taken just once daily.

Zafirlukast blocks the action of the cysteinyl leukotrienes on the CysLT1 receptors, thus reducing constriction of the airways, build-up of mucus in the lungs and inflammation of the breathing passages.

Indication

For the prophylaxis and chronic treatment of asthma.

Pharmacology

Zafirlukast is a synthetic, selective peptide leukotriene receptor antagonist (LTRA) 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.

Toxicity

Side effects include rash and upset stomach.

Affected Organisms

Humans and other mammals

Biotransformation

Hepatic

Absorption

Rapidly absorbed following oral administration, reduced following a high-fat or high-protein meal.

Half Life

10 hours

Protein Binding

99%

Elimination

The most common metabolic products are hydroxylated metabolites which are excreted in the feces.

Distribution

* 70 L

Clearance

* apparent oral cl=20 L/h
* 11.4 L/h [7-11 yrs]
* 9.2 L/h [5-6 yrs]

External Links

• [Wikipedia]

• [RxList]

• [Drugs.com]

Selleck Chemicals

S1633

Research Area: Cancer
Biological Activity:
Zafirlukast is in a class of medications called leukotriene receptor antagonists (LTRAs). It works by blocking the action of certain natural substances that cause swelling and tightening of the airways. [1] In a study, pranlukast or zafirlukast significantly inhibited 10 μM LTD4-evoked 35SO4 output in a concentration-dependent fashion, with maximal inhibitions of 83% at 10 μM pranlukast and 78% at 10 μM zafirlukast, and IC50 values of 0.3 μM for pranlukast and 0.6 μM for zafirlukast. [2] Both pranlukast and zafirlukast showed moderate inhibition of CYP2C9-catalysed tolbutamide 4-methylhydroxylation, competitively inhibiting tolbutamide 4-methylhydroxylation with estimated mean Ki values of 3.82 ± 0.50 and 5.86 ± 0.08 μM, respectively. [3] Zafirlukast inhibited the hydroxylation of tolbutamide (CYP2C9; mean IC50=7.0 µM). [4]

Sigma Aldrich

Z4152

Biochem/physiol Actions
Zafirlukast is a potent subtype specific cysteinyl leukotriene type 1 receptor (CysLT1) antagonist; antiasthmatic. Zafirlukast has over 1000-fold selectivity for CysLT1, one of two receptors for cysteinyl leukotrienes LTC4, LTD4, and LTE4, which are important mediators of human bronchial asthma.

TRC

Z125000

A potent, selective and orally active cysteinyl leukotriene type 1 receptor antagonist. Used as an antiasthmatic.

Molecule Details

References

PubChem Literature

From Data Sources

• Liu KH et al. Xenobiotica. 2004 May;34(5):429-38.

• Matassa, V.G., et al.: J. Med. Chem., 33, 1781 (1990)

• Dunn, C.J., Drugs, 61, 285 (1990)

• Krell, R.D., et al.: Am. Rev. Respir. Dis., 141, 978 (1990)

• Findlay, S.R., et al.: J. Allergy Clin. Immunol., 89, 1040 (1990)

• Matassa, V.G. et al., J. Med. Chem., 1990, 33, 1781, (synth, pharmacol)

• Adkins, J.C. et al., Drugs, 1998, 55, 121-144, (pharmacol, rev)

• Krell, R.D. et al., Am. Rev. Respir. Dis., 1990, 141, 978, (rev)

• Chung, K.F. et al., Drugs of Today (Barcelona), 1998, 34, 375-388, (rev, pharmacol)

• Eur. Pat., 1986, ICI, 199 543; CA, 106, 176163b, (synth, pharmacol)

• Taylor, I.K. et al., Lancet, 1991, 1, 690, (clin trial)

• Dunn, C.J. et al., Drugs, 2001, 61, 285-315, (rev)

• Dahlen, S.E. et al., Adv. Prostaglandin, Thromboxane, Leukotriene Res., 1990, 21, 461, (pharmacol)

References

Bioactivity

PubChem BioAssay

Bioactivity

Names and Identifiers

IUPAC Traditional name

Synonyms

IUPAC name

cyclopentyl N-[3-({2-methoxy-4-[(2-methylbenzenesulfonyl)carbamoyl]phenyl}methyl)-1-methyl-1H-indol-5-yl]carbamate

Brand Name

Accolate

API Name

Zafirlukast

International Nonproprietary Name (INN)

zafirlukast

Properties

Pharmacology Properties

Target

Respiratory Diseases

Mechanism of Action

Potent leukotriene D4 receptor antagonist (LTRA)

Safety Information

Product Information

Salt Data

Free Base

Purity

≥98% (HPLC)

Empirical Formula (Hill Notation)

C31H33N3O6S

Certificate of Analysis

Download link

Application(s)

Antiasthmatic agent

Related Proteins

PDB Bank

6RZ5

Molecule Details

DrugBank

DB00549

Drug Groups

approved; investigational

Description

Indication

For the prophylaxis and chronic treatment of asthma.

Pharmacology

Toxicity

Side effects include rash and upset stomach.

Affected Organisms

Humans and other mammals

Biotransformation

Hepatic

Absorption

Rapidly absorbed following oral administration, reduced following a high-fat or high-protein meal.

Half Life

10 hours

Protein Binding

99%

Elimination

The most common metabolic products are hydroxylated metabolites which are excreted in the feces.

Distribution

* 70 L

Clearance

* apparent oral cl=20 L/h
* 11.4 L/h [7-11 yrs]
* 9.2 L/h [5-6 yrs]

External Links

• [Wikipedia]

• [RxList]

• [Drugs.com]

Selleck Chemicals

S1633

Sigma Aldrich

Z4152

TRC

Z125000

A potent, selective and orally active cysteinyl leukotriene type 1 receptor antagonist. Used as an antiasthmatic.

References

PubChem Literature

From Data Sources

• Liu KH et al. Xenobiotica. 2004 May;34(5):429-38.

• Matassa, V.G., et al.: J. Med. Chem., 33, 1781 (1990)

• Dunn, C.J., Drugs, 61, 285 (1990)

• Krell, R.D., et al.: Am. Rev. Respir. Dis., 141, 978 (1990)

• Findlay, S.R., et al.: J. Allergy Clin. Immunol., 89, 1040 (1990)

• Matassa, V.G. et al., J. Med. Chem., 1990, 33, 1781, (synth, pharmacol)

• Adkins, J.C. et al., Drugs, 1998, 55, 121-144, (pharmacol, rev)

• Krell, R.D. et al., Am. Rev. Respir. Dis., 1990, 141, 978, (rev)

• Chung, K.F. et al., Drugs of Today (Barcelona), 1998, 34, 375-388, (rev, pharmacol)

• Eur. Pat., 1986, ICI, 199 543; CA, 106, 176163b, (synth, pharmacol)

• Taylor, I.K. et al., Lancet, 1991, 1, 690, (clin trial)

• Dunn, C.J. et al., Drugs, 2001, 61, 285-315, (rev)

• Dahlen, S.E. et al., Adv. Prostaglandin, Thromboxane, Leukotriene Res., 1990, 21, 461, (pharmacol)

Bioactivity

PubChem BioAssay

Molecule

ID:431