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

基本信息

化学结构

分子式

C₃₁H₃₃N₃O₆S

分子量

575.67522

精确质量

575.20900679

电荷

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

计算属性

JChem

LogD (pH = 7.4)

5.46

LogD (pH = 5.5)

5.62

Log P

6.40

可自由旋转的化学键

质子供体

质子受体

里宾斯基五规则

false

Acid pKa

4.29

极化表面积

115.73

极化性

61.93

摩尔折射率

158.58

LOG S

-6.09

数据来源

名称和标识

IUPAC传统名

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

别名

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标准名

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

商标名

Accolate

API名称

Zafirlukast

国际非专利药品(INN)

zafirlukast

名称和标识

数据登录号

化合物性质

药理学性质

作用靶点

Respiratory Diseases

生物活性机理

Potent leukotriene D4 receptor antagonist (LTRA)

产品相关信息

成盐信息

Free Base

Empirical Formula (Hill Notation)

C31H33N3O6S

纯度

≥98% (HPLC)

质检报告

下载链接

应用领域

Antiasthmatic agent

化合物性质

分子相关蛋白质

PDB Bank

6RZ5

分子相关蛋白质

分子图谱

暂无数据

点击上传数据

描述信息

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.

描述信息

参考文献

PubChem文献

数据源提供

• 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)

参考文献

生物活性

PubChem BioAssay

生物活性

名称和标识

IUPAC传统名

别名

IUPAC标准名

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

商标名

Accolate

API名称

Zafirlukast

国际非专利药品(INN)

zafirlukast

化合物性质

药理学性质

作用靶点

Respiratory Diseases

生物活性机理

Potent leukotriene D4 receptor antagonist (LTRA)

产品相关信息

成盐信息

Free Base

Empirical Formula (Hill Notation)

C31H33N3O6S

纯度

≥98% (HPLC)

质检报告

下载链接

应用领域

Antiasthmatic agent

分子相关蛋白质

PDB Bank

6RZ5

描述信息

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.

参考文献

PubChem文献

数据源提供

• 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)

生物活性

PubChem BioAssay

化合物信息

ID:431