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Zileuton

CAS No.
111406-87-2
Chemical Name:
Zileuton
Synonyms
ZYFLO;Zyfl;Leutml;ABT-077;Leutrol; A-64077;ZILEUTON;CGS-23622;Griluto-CR;AKOS 91253
CBNumber:
CB1344903
Molecular Formula:
C11H12N2O2S
Molecular Weight:
236.29
MDL Number:
MFCD00866097
MOL File:
111406-87-2.mol
MSDS File:
SDS
Last updated:2023-06-30 15:45:59

Zileuton Properties

Melting point 157-158°C
Boiling point 449.4±47.0 °C(Predicted)
Density 1.401±0.06 g/cm3(Predicted)
storage temp. room temp
solubility DMSO: ≥20mg/mL at ~60°C (warm up to 60 C for 5min)
pka pKa 10.3(H2O t undefined I undefined) (Uncertain)
form powder
color white to off-white
Stability Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month.
CAS DataBase Reference 111406-87-2(CAS DataBase Reference)
NCI Dictionary of Cancer Terms zileuton
FDA UNII V1L22WVE2S
NCI Drug Dictionary zileuton
Proposition 65 List Zileuton

SAFETY

Risk and Safety Statements

Symbol(GHS)  GHS hazard pictogramsGHS hazard pictograms
GHS07,GHS08
Signal word  Warning
Hazard statements  H302-H361d
Precautionary statements  P202-P264-P270-P280-P301+P312-P308+P313
Hazard Codes  Xn
Risk Statements  22-36
Safety Statements  26
WGK Germany  1
HS Code  2934990002
NFPA 704
0
2 0

Zileuton price More Price(54)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Sigma-Aldrich Z4277 Zileuton ≥98% (HPLC) 111406-87-2 10mg $84.1 2024-03-01 Buy
Sigma-Aldrich PHR2555 Zileuton 111406-87-2 200MG $186 2024-03-01 Buy
Sigma-Aldrich 1724656 Zileuton United States Pharmacopeia (USP) Reference Standard 111406-87-2 150mg $436 2024-03-01 Buy
Cayman Chemical 10006967 Zileuton >98% 111406-87-2 5mg $21 2024-03-01 Buy
Cayman Chemical 10006967 Zileuton >98% 111406-87-2 10mg $38 2024-03-01 Buy
Product number Packaging Price Buy
Z4277 10mg $84.1 Buy
PHR2555 200MG $186 Buy
1724656 150mg $436 Buy
10006967 5mg $21 Buy
10006967 10mg $38 Buy

Zileuton Chemical Properties,Uses,Production

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.

References

[1] A Rossi, C Pergola, A Koeberle, M Hoffmann, F Dehm, P Bramanti, S Cuzzocrea, O Werz and L Sautebin, The 5-lipoxygenase inhibitor, zileuton, suppresses prostaglandin biosynthesis by inhibition of arachidonic acid release in macrophages, British Journal of Pharmacology, 2010, col. 161, 555-570
[2] SE Wenzel and AK Kamada, Zileuton: the first 5-lipoxygenase inhibitor for the treatment of asthma, Ann Pharmacother., 1996, vol. 30, 858-864

Description

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.

Description

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%.

Chemical Properties

Crystalline Solid

Originator

Abbott (US)

Uses

An inhibitor of 5-lipoxygenase, the initial enzyme in the biosynthesis of leukotrienes from Arachidonic Acid. Used as an antiasthmatic.

Uses

gastric acid secretion inhibitor

Definition

ChEBI: A member of the class of 1-benzothiophenes that is 1-benzothiophene in which the hydrogen at position 2 is replaced by a 1-[carbamoyl(hydroxy)amino]ethyl group. A selective 5-lipoxygenase inhibitor, it inhibits the formation of leukotrienes LTB4, LTC4, LDT , and LTE4. It is used for the management of chronic asthma.

Manufacturing Process

N-Hydroxy-N-(1-benzo[b]thien-2-ylethyl) acetamide
1. 2-Acetyl benzo[b]thiophene.
Method a. Benzo[b]thiophene (10 g, 75 mmole) was dissolved in THF (50 ml) and cooled to -78°C. n-Butyl lithium (28 ml, 2.7 M in hexanes) was added. The mixture was stirred for 15 minutes and N,O-dimethyl acetohydroxamic acid was added. Following an additional 30 minutes of stirring, the reaction was quenched at -78°C with ethanol and 2 N HCl solution and extracted into ether. The solvent was removed in vacuo and the residue chromatographed on silica gel eluting with 20% ether in pentane to yield 6.9 g of the desired product as a white solid.
Method b. To a solution of benzo[b]thiophene (10.0 g, 75 mmole) in THF (50 ml) was added n-butyl lithium (33 ml, 2.5 M in hexanes) at -70°C under N 2 . The mixture, containing a white precipitate, was stirred at 70°C for 1 hour. Acetaldehyde (4.6 ml, 82 mmole) was added dropwise. After a few minutes the reaction was quenched with saturated NH 4 Cl solution. The layers were separated, the organic layer dried over MgSO4, filtered, and evaporated to give a white solid (10 g) which was used directly for the next step.
The alcohol prepared as described above (1.0 g) in acetone (50 ml) was cooled to 5°C and Jones Reagent was added dropwise until the orange yellow color persisted (1.4 ml). The reaction mixture was diluted with water and the desired product precipitated. It was collected by filtration to give 0.85 g.
2. 2-Acetyl benzo[b]thiophene oxime.
2-Acetyl benzo[b]thiophene (5 g, 28.4 mmole), prepared as described in step 1 above, and hydroxylamine hydrochloride (3.0 g, 42.6 mmole) were dissolved in a mixture of ethanol (50 ml) and pyridine (50 ml) and allowed to stir at room temperature for 2 hours. Most of the solvent was removed in vacuo and the residue dissolved in ether. After washing with 2 N HCl (100 ml), the solution was dried over MgSO 4 and evaporated. A white crystalline solid was obtained and was carried on without further purification. An alternative work-up may also be used. The reaction mixture was diluted with water (300 ml) and the product precipitated. It was filtered off and dried in vacuo.
3. 1-Benzo[b]thien-2-ylethyl hydroxylamine. The oxime prepared as in step 2 above (3.5 g, 18.5 mmole) was dissolved in ethanol (25 ml) and cooled to 0°C. Borane pyridine complex (3.7 ml, 37 mmole) was added via syringe under nitrogen followed 10 minutes later by 20% HCl in ethanol (30 ml). Within 30 minutes the reaction was complete and was brought to pH 9 with the addition of solid sodium carbonate or 2 N NaOH. The mixture was extracted into ether and dried over MgSO 4 . After evaporation a white solid (3.0 g) was obtained. This was carried on without further purification.
N-Hydroxy-N-(1-benzo[b]thien-2-ylethyl)urea
Method A. 1-Benzo[b]thien-2-yl ethyl hydroxyl amine prepared as described above, step 3 (2.0 g, 10 mmole), was refluxed for 30 minutes with trimethylsilyl isocyanate (1.65, 14.2 mmole) in dioxane (30 ml). The reaction mixture was then washed with saturated NH 4 Cl solution, dried with MgSO 4 , and evaporated.
Method B. 1-Benzo[b]thien-2-yl ethyl hydroxyl amine prepared as described in step 3, was dissolved in toluene (100 ml) and HCl gas was bubbled through the mixture at a moderate rate for about 4 minutes. The solution was then heated to reflux and phosgene was bubbled through for another 4 minutes. After an additional one hour reflux, the mixture was allowed to cool to room temperature and then added to excess cold ammonium hydroxide solution. The precipitate was collected and recrystallized. Melting point: 157°-158°C. NMR (300 MHz), and mass spectrum confirmed the structure of the prepared compound.

brand name

Zyflo (Sensus).

Therapeutic Function

Antiallergic, Antiinflammatory

Biological Activity

Orally active 5-lipoxygenase (5-LOX) inhibitor that inhibits LTB 4 synthesis (IC 50 values are 0.56, 2.3 and 2.6 μ M in dog, rat and human blood respectively). Inhibits antigen-induced contraction of tracheal strips in vitro (IC 50 = 6 μ M) and exhibits antiasthmatic activity in vivo . Also weakly inhibits CYP1A2 (K i = 66 - 98 μ M).

Biochem/physiol Actions

Zileuton is an anti-asthmatic, an inhibitor of 5-lipoxygenase; the initial enzyme in the biosynthesis of leukotrienes from arachidonic acid.

storage

Store at +4°C

References

1) Carter et al. (1991), 5-Lipoxygense inhibitory activity of zileuton; J. Pharmacol. Exp. Ther. 256 929 2) Rossi et al. (2010), The 5-lipoxygenase inhibitor, zileuton, suppresses prostaglandin biosynthesis by inhibition of arachidonic acid release in macrophages; Br. J. Pharmacol. 161 555

Zileuton Preparation Products And Raw materials

Global( 343)Suppliers
Supplier Tel Email Country ProdList Advantage
Capot Chemical Co.,Ltd.
571-85586718 +8613336195806 sales@capotchem.com China 29797 60
Henan Tianfu Chemical Co.,Ltd.
+86-0371-55170693 +86-19937530512 info@tianfuchem.com China 21703 55
ATK CHEMICAL COMPANY LIMITED
+undefined-21-51877795 ivan@atkchemical.com China 32480 60
career henan chemical co
+86-0371-86658258 sales@coreychem.com China 29919 58
Hubei Jusheng Technology Co.,Ltd.
18871490254 linda@hubeijusheng.com CHINA 28180 58
Hubei xin bonus chemical co. LTD
86-13657291602 linda@hubeijusheng.com CHINA 22968 58
Chongqing Chemdad Co., Ltd
+86-023-61398051 +8613650506873 sales@chemdad.com China 39916 58
Alchem Pharmtech,Inc.
8485655694 sales@alchempharmtech.com United States 63711 58
CONIER CHEM AND PHARMA LIMITED
+8618523575427 sales@conier.com China 47464 58
Shaanxi Dideu Medichem Co. Ltd
18192627656 1012@dideu.com China 3911 58

View Lastest Price from Zileuton manufacturers

Image Update time Product Price Min. Order Purity Supply Ability Manufacturer
Zileuton pictures 2021-11-15 Zileuton
111406-87-2
US $0.00 / KG 1KG 99% 200000pcs Qiuxian Baitai New Material Co., LTD
Zileuton pictures 2021-08-12 Zileuton
111406-87-2
US $15.00-10.00 / KG 1KG 99%+ HPLC Monthly supply of 1 ton Zhuozhou Wenxi import and Export Co., Ltd
Zileuton pictures 2021-07-13 Zileuton
111406-87-2
US $15.00-10.00 / KG 1KG 99%+ HPLC Monthly supply of 1 ton Zhuozhou Wenxi import and Export Co., Ltd
  • Zileuton pictures
  • Zileuton
    111406-87-2
  • US $0.00 / KG
  • 99%
  • Qiuxian Baitai New Material Co., LTD
  • Zileuton pictures
  • Zileuton
    111406-87-2
  • US $15.00-10.00 / KG
  • 99%+ HPLC
  • Zhuozhou Wenxi import and Export Co., Ltd
  • Zileuton pictures
  • Zileuton
    111406-87-2
  • US $15.00-10.00 / KG
  • 99%+ HPLC
  • Zhuozhou Wenxi import and Export Co., Ltd

Zileuton Spectrum

Zileuton and its intermediates A-64077 Abbott 64077 Leutrol Zyfl 1-(1-(BENZO[B]THIOPHEN-2-YL)ETHYL)-1-HYDROXYUREA Leutml N-(1-Benzolb]thien-2-ylethyl)。N-hydroxyurea 1-[1-(1-Benzothiophen-2-yl)ethyl]-1-hydroxyurea 1-Hydroxy-1-[1-(benzo[b]thiophene-2-yl)ethyl]urea ABT-077 CGS-23622 Zileuton (150 mg) ZYFLO (zileuton) 1-[(1S)-1-(1-benzothiophen-2-yl)ethyl]-1-hydroxyurea N-(1-bezo[b]thien-2-yl-ethyl)-N-hydroxy-urea Griluto-CR Zileuton 1-(1-Benzothiophen-2-ylethyl)-1-hydroxy-urea Zileuton, >=99% Zileuton (Zilpaterol) ZILEUTON AKOS 91253 1-(1-benzothiophen-2-ylethyl)-1-hydroxy-urea Qi Liu Tong High quality USP 39/EP 9.0 /BP 2012 GMP DMF FDA Zileuton producer Zileuton USP/EP/BP Zileuton (A 64077 ZileutonQ: What is Zileuton Q: What is the CAS Number of Zileuton Q: What is the storage condition of Zileuton Q: What are the applications of Zileuton "Zileuton-13C2,15N" Zileuton (1724656) ZYFLO 111406-87-2 11406-87-2 All Inhibitors Inhibitors Intermediates & Fine Chemicals Pharmaceuticals Amines Aromatics Active Pharmaceutical Ingredients Antiasthmatic ACIPHEX Other APIs API