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

• ChemBase编号: 431
• 分子式: C31H33N3O6S
• 平均质量: 575.67522
• 单一同位素质量: 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

名称和登记号

名称

• IUPAC标准名: cyclopentyl N-[3-({2-methoxy-4-[(2-methylbenzenesulfonyl)carbamoyl]phenyl}methyl)-1-methyl-1H-indol-5-yl]carbamate
• 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
• 商标名: Accolate
• 别名: 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

登记号

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

理论计算性质

JChem

• Acid pKa: 4.285297
• 质子受体: 6
• 质子供体: 2
• LogD (pH = 5.5): 5.621156
• LogD (pH = 7.4): 5.4633803
• Log P: 6.4037447
• 摩尔折射率: 158.5769 cm^3
• 极化性: 61.699852 Å^3
• 极化表面积: 115.73 Å^2
• 可自由旋转的化学键: 8
• 里宾斯基五规则: false

ALOGPS 2.1

• Log P: 4.84
• LOG S: -5.78
• 溶解度: 9.62e-04 g/l

分子性质

理化性质

• 溶解度: Chlorloform; DMSO: ≥28 mg/mL
• 外观: Pale Pink Solid; solid
• 熔点: 190-193°C
• 疏水性(logP): 5.4

安全信息

• 保存条件: -20°C; Refrigerator
• 德国WGK号: 3
• GHS危险声明: H413
• 保存温度: room temp

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

• 纯度: ≥98% (HPLC)
• 成盐信息: Free Base
• 应用领域: Antiasthmatic agent
• Empirical Formula (Hill Notation): C31H33N3O6S

详细说明

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.

参考文献

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