Zileuton

Base Information

• Chemical Name: Zileuton
• CAS No.: 111406-87-2
• Deprecated CAS: 133305-01-8,154003-29-9
• Molecular Formula: C₁₁H₁₂N₂O₂S
• Molecular Weight: 236.294
• Hs Code.: 2934990002
• European Community (EC) Number: 601-087-3
• NSC Number: 759277,730712
• UNII: V1L22WVE2S
• DSSTox Substance ID: DTXSID9023752
• Nikkaji Number: J369.927G
• Wikipedia: Zileuton
• Wikidata: Q202998
• NCI Thesaurus Code: C26667
• RXCUI: 40575
• Pharos Ligand ID: 96L5WFP1BGGT
• Metabolomics Workbench ID: 43046
• ChEMBL ID: CHEMBL93
• Mol file: 111406-87-2.mol

Synonyms:A 64077;A-64077;Abbot 64077;N-(1-benzo(b)thien-2-ylethyl)-N-hydroxyurea;zileuton;Zyflo

Chemical Property of Zileuton

Chemical Property:

• Appearance/Colour: crystalline solid
• Vapor Pressure: 7.29E-09mmHg at 25°C
• Melting Point: 157-158 °C
• Refractive Index: 1.704
• Boiling Point: 449.4 °C at 760 mmHg
• PKA: pKa 10.3(H2O t undefined I undefined) (Uncertain)
• Flash Point: 225.6 °C
• PSA: 94.80000
• Density: 1.401 g/cm³
• LogP: 3.43250
• Storage Temp.: Store at +4°C
• Solubility.: DMSO: ≥20mg/mL at ~60°C (warm up to 60 C for 5min)
• XLogP3: 1.6
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 2
• Exact Mass: 236.06194880
• Heavy Atom Count: 16
• Complexity: 275

Purity/Quality:

99% ^*data from raw suppliers

Zileuton ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn
• Statements: 22-36
• Safety Statements: 26

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antiasthmatic Agents
• Canonical SMILES: CC(C1=CC2=CC=CC=C2S1)N(C(=O)N)O
• Recent ClinicalTrials: Aspirin and Zileuton and Biomarker Expression in Nasal Tissue of Current Smokers
• Recent EU Clinical Trials: Application of zileuton (Zyflo CR) in patients with Sj?gren Larsson Syndrome
• Description: Zileuton, a benzothiophene N-hydroxyurea, is the only approved inhibitor of 5-lipoxygenase. It is believed to intervene with allergic and inflammatory diseases by suppression of leukotriene (LT) biosynthesis. The compound belongs to the class of iron ligand-type inhibitors of 5-lipoxygenase that not only chelates the active site iron of the enzyme but also possesses weak-reducing properties. Zileuton is used as a type of drug for the prophylaxis and chronic treatment of asthma. Zileuton is a reversible 5-lipoxygenase (5-LO) inhibitor. It inhibits 5-LO activity in rat basophilic leukemia-1 (RBL-1) cell supernatant with an IC50 value of 0.5 μM. Zileuton inhibits leukotriene B4 (LTB4; ) production induced by the calcium ionophore A23187 in purified human peripheral blood polymorphonuclear leukocytes (PMNLs; IC50 = 0.6 μM). Zileuton (10 mg/kg, p.o.) prevents antigen challenge-induced increases in specific lung resistance in a sheep model of asthma at 4 to 8 hours post-challenge following administration 2 hours pre-challenge. Formulations containing zileuton have been used in the prophylaxis and chronic treatment of asthma. Zyflo was launched in the US for chronic asthma. It can be prepared in three steps from 2-acetylbenzo[b]thiophene. Zyflo is a reversible direct inhibitor of 5- lipoxgenase that is orally-active. It was able to effect a 70-100 YO reduction in LTB4, LTE4, LTD4 and LTC4. Zyflo has no effect on myeloperoxidase activity, neutrophil degranulation, mast cell histamine release or phospholipase A2 activities. It did not inhibit cyclooxygenase as witnessed by the formation of TXB2. It significantly attentuated asthmatic response to cold dry air, inhibited exercise-induce bronchoconstriction, and attenuated induced bronchospasms. Zyflo has antiinflammatory effects as witnessed by a decrease in edema, mucus production and cellular infiltration. It had a bronchodilatory effect within 2 h and increased spirometry results by 18%.
• Uses: An inhibitor of 5-lipoxygenase, the initial enzyme in the biosynthesis of leukotrienes from Arachidonic Acid. Used as an antiasthmatic gastric acid secretion inhibitor An inhibitor of 5-lipoxygenase, the initial enzyme in the biosynthesis of leukotrienes from Arachidonic Acid. Used as an antiasthmatic.
• Therapeutic Function: Antiallergic, Antiinflammatory

Technology Process of Zileuton

There total 18 articles about Zileuton 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: 92.0%

N-(1-benzo[b]thien-2ylethyl)-O-(tetrahydropyran-2yl)-N-hydroxyurea → zileuton (142606-21-1,143200-94-6,111406-87-2)

Guidance literature:

In hydrogenchloride; ethanol;

Reference yield: 88.0%

2-acetyl benzo[b]thiophene (22720-75-8) + hydroxylamine (7803-49-8) + methyl carbamate (598-55-0) → zileuton (142606-21-1,143200-94-6,111406-87-2)

Guidance literature:

hydroxylamine; methyl carbamate; With sodium hydroxide; In water; at 5 - 30 ℃;

2-acetyl benzo[b]thiophene; With methanol; sodium tetrahydroborate; In tetrahydrofuran; water; at 10 - 40 ℃;

With hydrogenchloride; acetic acid; at 40 - 45 ℃; for 3h;

Reference yield: 82.0%

1-(benzo[b]thiophen-2-yl)ethanol (51868-95-2) + N-hydroxyurea (127-07-1) → zileuton (142606-21-1,143200-94-6,111406-87-2)

Guidance literature:

With potassium hydrogensulfate; acetic acid; In water; at 40 - 45 ℃; for 6h; Product distribution / selectivity;

upstream raw materials:

trimethylsilyl isocyanate

1-(N-hydroxyamino)-1-(benzothien-2-yl)ethane

C₂₂H₂₃NO₅S

N,O-bis(phenoxycarbonyl)-N-(1-benzothien-2-ylethyl)hydroxylamine

Downstream raw materials:

N-hydroxy-N-(1-benzo[b]thien-2-ylethyl) urea sodium salt

Refernces

• 1、 Copp,Fohey,Lannoye. "Acid-catalyzed addition of N-hydroxyurea to 1-aryl alcohol derivatives: A new synthesis of Zileuton". . p. 3081 - 3086. Retrieved 2001.
• 2、 -. "IMPROVED PROCESS FOR THE PREPARATION OF (±)-1-(1-BENZO[B]THIEN-2-YLETHYL)-1-HYDROXYUREA". Page/Page column 20. . Retrieved 2011/04/24.