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

• ChemBase ID: 431
• Molecular Formular: C31H33N3O6S
• Molecular Mass: 575.67522
• Monoisotopic Mass: 575.20900679
• SMILES: S(=O)(=O)(NC(=O)c1cc(OC)c(Cc2c3c(n(c2)C)ccc(NC(=O)OC2CCCC2)c3)cc1)c1c(cccc1)C
• Canonical SMILES: COc1cc(ccc1Cc1cn(c2c1cc(cc2)NC(=O)OC1CCCC1)C)C(=O)NS(=O)(=O)c1ccccc1C
• 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

NAMES AND DATABASE IDS

Names

• IUPAC name: cyclopentyl N-[3-({2-methoxy-4-[(2-methylbenzenesulfonyl)carbamoyl]phenyl}methyl)-1-methyl-1H-indol-5-yl]carbamate
• 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
• Brand Name: Accolate
• Synonyms: zafirlukast; Zafirlukast; N-[3-[[2-Methoxy-4-[[[(2-methylphenyl)sulfonyl]amino]carbonyl]phenyl]methyl]-1-methyl-1H-indol-5-yl]carbamic acid cyclopentyl ester; Zafirlukast; [3-[[2-Methoxy-4-[[[(2-methylphenyl)sulfonyl]amino]carbonyl]phenyl]methyl]-1-methyl-1H-indol-5-yl]carbamic Acid Cyclopentyl Ester; ICI-2204219; Accolate; Vanticon

Database IDs

• CAS Number: 107753-78-6
• MDL Number: MFCD00864775
• PubChem SID: 160963894; 46506874
• PubChem CID: 5717

CALCULATED PROPERTIES

JChem

• Acid pKa: 4.285297
• H Acceptors: 6
• H Donor: 2
• LogD (pH = 5.5): 5.621156
• LogD (pH = 7.4): 5.4633803
• Log P: 6.4037447
• Molar Refractivity: 158.5769 cm^3
• Polarizability: 61.699852 Å^3
• Polar Surface Area: 115.73 Å^2
• Rotatable Bonds: 8
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 4.84
• LOG S: -5.78
• Solubility (Water): 9.62e-04 g/l

PROPERTIES

Physical Property

• Solubility: Chlorloform; DMSO: ≥28 mg/mL
• Apperance: Pale Pink Solid; solid
• Melting Point: 190-193°C
• Hydrophobicity(logP): 5.4

Safety Information

• Storage Condition: -20°C; Refrigerator
• German water hazard class: 3
• GHS Hazard statements: H413
• Storage Temperature: room temp

Pharmacology Properties

• Target: Respiratory Diseases
• Mechanism of Action: Potent leukotriene D4 receptor antagonist (LTRA)

Product Information

• Purity: ≥98% (HPLC)
• Salt Data: Free Base
• Application(s): Antiasthmatic agent
• Empirical Formula (Hill Notation): C31H33N3O6S

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.

Toronto Research Chemicals - Z125000

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

REFERENCES

• Liu KH et al. Xenobiotica. 2004 May;34(5):429-38.
• Matassa, V.G., et al.: J. Med. Chem., 33, 1781 (1990)
• Findlay, S.R., et al.: J. Allergy Clin. Immunol., 89, 1040 (1990)
• Krell, R.D., et al.: Am. Rev. Respir. Dis., 141, 978 (1990)
• Dunn, C.J., Drugs, 61, 285 (1990)
• Eur. Pat., 1986, ICI, 199 543; CA, 106, 176163b, (synth, pharmacol)
• Dahlen, S.E. et al., Adv. Prostaglandin, Thromboxane, Leukotriene Res., 1990, 21, 461, (pharmacol)
• Krell, R.D. et al., Am. Rev. Respir. Dis., 1990, 141, 978, (rev)
• Matassa, V.G. et al., J. Med. Chem., 1990, 33, 1781, (synth, pharmacol)
• Taylor, I.K. et al., Lancet, 1991, 1, 690, (clin trial)
• Adkins, J.C. et al., Drugs, 1998, 55, 121-144, (pharmacol, rev)
• Chung, K.F. et al., Drugs of Today (Barcelona), 1998, 34, 375-388, (rev, pharmacol)
• Dunn, C.J. et al., Drugs, 2001, 61, 285-315, (rev)