Ethyl 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylate
[CAS# 160844-75-7]

Identification

• Classification: Organic raw materials >> Carboxylic compounds and derivatives >> Carboxylic esters and their derivatives
• Name: Ethyl 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylate
• Molecular Formula: C₁₈H₂₀N₂O₃S
• Molecular Weight: 344.43
• CAS Registry Number: 160844-75-7
• EC Number: 927-913-5
• SMILES: CCOC(=O)C1=C(N=C(S1)C2=CC(=C(C=C2)OCC(C)C)C#N)C

Properties

• Density: 1.22

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H312-H315-H319-H332
• Safety Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P317-P321-P330-P332+P317-P337+P317-P362+P364-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Acute toxicity	Acute Tox.	4	H312
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	4	H332

Discovery and Applications

Ethyl 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylate, commonly known as Zafirlukast, was discovered through systematic drug design efforts targeting leukotriene receptors. Researchers at AstraZeneca synthesized a series of compounds to antagonize leukotriene receptors, aiming to develop novel anti-inflammatory agents for the treatment of asthma and other respiratory conditions. Zafirlukast emerged as a promising candidate due to its high affinity for leukotriene receptors, particularly the cysteinyl leukotriene receptor type 1 (CysLT1). Its ability to selectively block the action of leukotrienes, potent mediators of inflammation, marked a significant advancement in the treatment of asthma and allergic rhinitis.

Zafirlukast is used as a controller medication in the management of asthma to prevent and control airway inflammation. By antagonizing CysLT1 receptors, it inhibits the bronchoconstrictive and pro-inflammatory effects of leukotrienes, leading to improved airflow and reduced asthma symptoms. Zafirlukast is indicated for long-term maintenance therapy in patients with chronic asthma, particularly those with mild to moderate persistent asthma who require additional control beyond bronchodilator therapy. It helps reduce the frequency and severity of asthma exacerbations and improves overall lung function.

Zafirlukast is also used in the treatment of allergic rhinitis to alleviate nasal congestion, sneezing, and itching associated with allergic inflammation. By blocking the action of leukotrienes, it reduces nasal congestion and improves nasal airflow, providing relief from allergic symptoms. Zafirlukast may be used as an adjunctive therapy in combination with antihistamines or intranasal corticosteroids for the management of moderate to severe allergic rhinitis. Its anti-inflammatory properties complement the effects of other allergy medications, offering comprehensive symptom control.

Zafirlukast is effective in preventing exercise-induced bronchoconstriction (EIB), a transient narrowing of the airways triggered by physical exertion. By inhibiting leukotriene-mediated inflammation and bronchoconstriction, it helps athletes and individuals with EIB engage in physical activity without experiencing asthma symptoms.

Zafirlukast is available in oral tablet form for convenient administration. Patients are typically instructed to take it once or twice daily, with or without food, to maintain therapeutic blood levels. While generally well-tolerated, zafirlukast may cause adverse effects such as headache, gastrointestinal upset, and liver enzyme abnormalities. Patients should be monitored for signs of liver dysfunction, especially during the initial stages of treatment. Zafirlukast may interact with other medications, particularly those metabolized by the cytochrome P450 enzyme system. Healthcare providers should review patients' medication profiles and consider potential drug interactions before initiating zafirlukast therapy.

References

2020. Simple and Rapid Micellar Electrokinetic Chromatography Method for Simultaneous Determination of Febuxostat and its Related Impurities. Chromatographia, 83(10), 1199-1207.
DOI: 10.1007/s10337-020-03919-7

2009. 2-[3-Cyano-4-(2-methyl-prop-oxy)phen-yl]-4-methyl-thia-zole-5-carboxylic acid pyridine solvate. Acta crystallographica. Section E, Structure reports online, 65(11), o2727.
DOI: 10.1107/s1600536809039002