Zafirlukast

Base Information

• Chemical Name: Zafirlukast
• CAS No.: 107753-78-6
• Molecular Formula: C31H33N3O6S
• Molecular Weight: 575.686
• European Community (EC) Number: 663-705-8
• UNII: XZ629S5L50
• DSSTox Substance ID: DTXSID5023746
• Nikkaji Number: J322.324H
• Wikipedia: Zafirlukast
• Wikidata: Q928378
• NCI Thesaurus Code: C47785
• RXCUI: 114970
• Pharos Ligand ID: GJ5ZBJBGBWFX
• Metabolomics Workbench ID: 42885
• ChEMBL ID: CHEMBL603
• Mol file: 107753-78-6.mol

Synonyms:4-(5-cyclopentyloxycarbonylamino-2-methylindol-3-yl-methyl)-3-methoxy-N-O-tolylsulfonylbenzamide;Accolate;Aeronix;ICI 204,219;ICI 204219;ICI-204219;Olmoran;zafirlukast

Chemical Property of Zafirlukast

Chemical Property:

• Appearance/Colour: Off-white to pale pink crystalline solid
• Melting Point: 139 ºC
• Refractive Index: 1.64
• PKA: 4.94±0.10(Predicted)
• PSA: 131.09000
• Density: 1.32 g/cm³
• LogP: 7.36510
• Storage Temp.: Refrigerator
• Solubility.: DMSO: ≥28mg/mL
• XLogP3: 5.5
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 9
• Exact Mass: 575.20900695
• Heavy Atom Count: 41
• Complexity: 1010

Purity/Quality:

99%min ^*data from raw suppliers

Zafirlukast ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antiasthma Agents
• Canonical SMILES: CC1=CC=CC=C1S(=O)(=O)NC(=O)C2=CC(=C(C=C2)CC3=CN(C4=C3C=C(C=C4)NC(=O)OC5CCCC5)C)OC
• Recent ClinicalTrials: Zafirlukast in Treatment of Marker Relapsed Ovarian Cancer
• Indications: Clinically suitable for the prevention and treatment of chronic mild to moderate asthma, especially for patients with aspirin or aspirin asthma, or with upper respiratory tract diseases (such as nasal polyps, allergic rhinitis), but not for the treatment of acute asthma. It is suitable for hormone-resistant asthma or asthmatic patients who refuse use of hormone. In cases of serious asthma, additional administration with this product can maintain control of asthma attacks or to reduce the amount of hormones.
• Description: Accolate was launched in Ireland, Finland and the US for treatment of asthma. Prepared via an eight step synthesis from methyl 3-methoxy-4- methylbenzoate, zafirlukast acts as a LTD4 antagonist and is the first compound of a new class of drugs. LTC4, LTD4 and LTE4 were determined to be the constituents of the slow-reacting substance of anaphylaxis (SRS-A) which was found to induce asthma effects (bronchoconstriction, increased vascular permeability resulting in edema, cellular infiltration of airway tissues and decreased mucociliary transport). Thus an inhibitor of their synthesis would at least attenuate these symptoms. Zafirlukast binds to the CysLT receptor LT-1 and blocks the effect of LTC4, LTD4 and LTE4. The drug is an oral twice daily formulation that reversed an LTD4 challenge, attenuated the response of platelet-activating factor (PAF), an allergen and cold air challenge and exercise-induced asthma.
• Uses: A potent, selective and orally active CysLT receptor antagonist. Leukotriene D4 antagonist. Used as an antiasthmatic antiasthmatic;leukotriene receptor antagonist (LTRA) Zafirlukast has been used to stimulate pancreatic β cell line (MIN6) and pancreatic islets for insulin secretion assay. It may be used as an adenosine triphosphate-binding cassette transporter (ABCG2) inhibitor in MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] cytotoxicity assay in human embryonic kidney cells (HEK293) and in Kirby-Bauer disc diffusion assays, bactericidal activity and minimal inhibitory concentration (mIC) assay against M. smegmatis
• Therapeutic Function: Anti-asthmatic
• Clinical Use: Zafirlukast is an indole derivative with a sulfonamide group that fulfills the need for an ionizable moiety on the pharmacophore. A large number of analogues have been prepared; however, they all resulted in a decrease in antagonist activity. Zafirlukast, like montelukast, is a selective antagonist for the cysLT1 receptor and antagonizes the bronchoconstrictive effects of all leukotrienes (LTC4, LTD4, and LTE4).
• Drug interactions: Potentially hazardous interactions with other drugs Aminophylline: possibly increases aminophylline concentration; zafirlukast concentration reduced. Analgesics: concentration increased by aspirin. Antibacterials: concentration reduced by erythromycin. Anticoagulants: may enhance the effects of warfarin. Theophylline: possibly increases theophylline concentration; zafirlukast concentration reduced.

Technology Process of Zafirlukast

There total 27 articles about Zafirlukast which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 89.0%

N1-{3-methoxy-4-(N-methyl-5-nitro-1H-3-indolyl)methylbenzoyl}-2-methyl-1-benzenesulfonamide + cyclopentyl chloroformate (50715-28-1) → ZAFIRLUKAST (107753-78-6)

Guidance literature:

N₁-{3-methoxy-4-(N-methyl-5-nitro-1H-3-indolyl)methylbenzoyl}-2-methyl-1-benzenesulfonamide; With hydrogen; In methanol; at 20 ℃; for 2h;

cyclopentyl chloroformate; With 4-methyl-morpholine; In dichloromethane; at 0 - 20 ℃; for 3h;

Reference yield: 89.0%

N1-{4-[(5-amino-N-methyl-1H-3-indolyl)methyl]-3-methoxybenzoyl}-2-methyl-1-benzenesulfonamide + cyclopentyl chloroformate (50715-28-1) → ZAFIRLUKAST (107753-78-6)

Guidance literature:

With 4-methyl-morpholine; In dichloromethane; at 25 - 35 ℃; for 0.5h; Inert atmosphere;

DOI:10.1021/op049869i

Reference yield: 86.0%

methyl 2-(aminosulfonyl)benzoate (88-19-7) + 4-[5-(cyclopentyloxycarbonylamino)-1-methyl-indol-3-yl-methyl]-3-methoxy-benzoic acid (107754-20-1) → ZAFIRLUKAST (107753-78-6)

Guidance literature:

With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 25 - 35 ℃;

DOI:10.1021/op800137b

upstream raw materials:

methyl 2-(aminosulfonyl)benzoate

4-[5-(cyclopentyloxycarbonylamino)-1-methyl-indol-3-yl-methyl]-3-methoxy-benzoic acid

cyclopentyl chloroformate

methyl 4-(bromomethyl)-3-methoxybenzoate

Refernces

• 1、 Ancell, Claire L.,Derrick, Ian,Moseley, Jonathan D.,Stott, Jeffery A.. "Investigation into the acidification process of zafirluskast nitroacid leads to a surprising improvement in product quality". . p. 808 - 813. Retrieved 2004.
• 2、 -. "PROCESS FOR THE PREPARATION OF ZAFIRLUKAST AND ANALOGS THEREOF". . . Retrieved 2019/07/17.
• 3、 Goverdhan, Gilla,Reddy, Anumula Raghupathi,Sampath, Aalla,Srinivas, Kurella,Himabindu, Vurimidi,Reddy, Ghanta Mahesh. "An improved and scalable process for zafirlukast: An asthma drug". experimental part. p. 67 - 72. Retrieved 2010/04/22.