Tìm theo
Zileuton
Các tên gọi khác (8 ) :
  • (+-)-1-(1-Benzo[b]thien-2-ylethyl)-1-hydroxyurea
  • Leutrol
  • N-(1-Benzo(b)thien-2-ylethyl)-N-hydroxyurea
  • N-[1-(Benzo[b]thiophen-2-yl)ethyl]-N-hydroxyurea
  • Zileuton
  • Zileuton
  • Zileutonum
  • Zyflo
anti inflammatory agents non steroidal, lipoxygenase inhibitors, leukotriene antagonists
Thuốc Gốc
Small Molecule
CAS: 111406-87-2
ĐG : Cornerstone Pharmacy , http://www.cpsrx.com
CTHH: C11H12N2O2S
PTK: 236.29
Leukotrienes are substances that induce numerous biological effects including augmentation of neutrophil and eosinophil migration, neutrophil and monocyte aggregation, leukocyte adhesion, increased capillary permeability, and smooth muscle contraction. These effects contribute to inflammation, edema, mucus secretion, and bronchoconstriction in the airways of asthmatic patients. Zileuton relieves such symptoms through its selective inhibition of 5-lipoxygenase, the enzyme that catalyzes the formation of leukotrienes from arachidonic acid. Specifically, it inhibits leukotriene LTB4, LTC4, LTD4, and LTE4 formation. Both the R(+) and S(-) enantiomers are pharmacologically active as 5-lipoxygenase inhibitors in in vitro systems. The immediate release tablet of Zileuton has been withdrawn from the US market.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C11H12N2O2S
Phân tử khối
236.29
Monoisotopic mass
236.061948328
InChI
InChI=1S/C11H12N2O2S/c1-7(13(15)11(12)14)10-6-8-4-2-3-5-9(8)16-10/h2-7,15H,1H3,(H2,12,14)
InChI Key
InChIKey=MWLSOWXNZPKENC-UHFFFAOYSA-N
IUPAC Name
1-[1-(1-benzothiophen-2-yl)ethyl]-1-hydroxyurea
Traditional IUPAC Name
zileuton
SMILES
CC(N(O)C(N)=O)C1=CC2=CC=CC=C2S1
Độ tan chảy
144.2-145.2 °C
Độ hòa tan
Practically insoluble (0.5 mg/ml)
logP
0.9
logS
-3.6
pKa (strongest acidic)
8.84
pKa (Strongest Basic)
-5.5
PSA
66.56 Å2
Refractivity
61.96 m3·mol-1
Polarizability
24.14 Å3
Rotatable Bond Count
2
H Bond Acceptor Count
2
H Bond Donor Count
2
Physiological Charge
0
Number of Rings
2
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : Zileuton is an asthma drug that differs chemically and pharmacologically from other antiasthmatic agents. It blocks leukotriene synthesis by inhibiting 5-lipoxygenase, an enzyme of the eicosanoid synthesis pathway. Current data indicates that asthma is a chronic inflammatory disorder of the airways involving the production and activity of several endogenous inflammatory mediators, including leukotrienes. Sulfido-peptide leukotrienes (LTC4, LTD4, LTE4, also known as the slow-releasing substances of anaphylaxis) and LTB4, a chemoattractant for neutrophils and eosinophils, are derived from the initial unstable product of arachidonic acid metabolism, leukotriene A4 (LTA4), and can be measured in a number of biological fluids including bronchoalveolar lavage fluid (BALF) from asthmatic patients. In humans, pretreatment with zileuton attenuated bronchoconstriction caused by cold air challenge in patients with asthma.
Cơ Chế Tác Dụng : Leukotrienes are substances that induce numerous biological effects including augmentation of neutrophil and eosinophil migration, neutrophil and monocyte aggregation, leukocyte adhesion, increased capillary permeability, and smooth muscle contraction. These effects contribute to inflammation, edema, mucus secretion, and bronchoconstriction in the airways of asthmatic patients. Zileuton relieves such symptoms through its selective inhibition of 5-lipoxygenase, the enzyme that catalyzes the formation of leukotrienes from arachidonic acid. Specifically, it inhibits leukotriene LTB4, LTC4, LTD4, and LTE4 formation. Both the R(+) and S(-) enantiomers are pharmacologically active as 5-lipoxygenase inhibitors in in vitro systems. The immediate release tablet of Zileuton has been withdrawn from the US market. Leukotrienes are substances that induce numerous biological effects including augmentation of neutrophil and eosinophil migration, neutrophil and monocyte aggregation, leukocyte adhesion, increased capillary permeability, and smooth muscle contraction. These effects contribute to inflammation, edema, mucus secretion, and bronchoconstriction in the airways of asthmatic patients. Zileuton relieves such symptoms through its selective inhibition of 5-lipoxygenase, the enzyme that catalyzes the formation of leukotrienes from arachidonic acid. Specifically, it inhibits leukotriene LTB4, LTC4, LTD4, and LTE4 formation. Both the R(+) and S(-) enantiomers are pharmacologically active as 5-lipoxygenase inhibitors in in vitro systems. Due to the role of leukotrienes in the pathogenesis of asthma, modulation of leukotriene formation by interruption of 5-lipoxygenase activity may reduce airway symptoms, decrease bronchial smooth muscle tone, and improve asthma control.
Dược Động Học :
▧ Absorption :
Rapidly and almost completely absorbed. The absolute bioavailability is unknown.
▧ Volume of Distribution :
* 1.2 L/kg
▧ Protein binding :
93% bound to plasma proteins, primarily to albumin.
▧ Metabolism :
Hepatic. Zileuton and its N-dehydroxylated metabolite are oxidatively metabolized by the cytochrome P450 isoenzymes 1A2, 2C9 and 3A4.
▧ Route of Elimination :
Elimination of zileuton is predominantly via metabolism with a mean terminal half-life of 2.5 hours. The urinary excretion of the inactive N-dehydroxylated metabolite and unchanged zileuton each accounted for less than 0.5% of the dose.
▧ Half Life :
2.5 hours
▧ Clearance :
* Apparent oral cl=7 mL/min/kg
Độc Tính : The oral minimum lethal doses in mice and rats were 500-4000 and 300-1000 mg/kg in various preparations, respectively (providing greater than 3 and 9 times the systemic exposure [AUC] achieved at the maximum recommended human daily oral dose, respectively).
Chỉ Định : For the prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older.
Tương Tác Thuốc :
  • Aminophylline Zileuton increases the effect and toxicity of theophylline
  • Bendamustine CYP1A2 metabolism may result in increased levels of active metabolites, decreases levels of bendamustine.
  • Dihydroergotamine Possible ergotism and severe ischemia with this combination
  • Eltrombopag Affects hepatic enzyme CYP1A2 metabolism and may increase the level of eltrombopag.
  • Ergotamine Possible ergotism and severe ischemia with this combination
  • Oxtriphylline Zileuton increases the effect and toxicity of theophylline
  • Pimozide Increased risk of cardiotoxicity and arrhythmias
  • Ramelteon Zileuton increases levels/toxicity of ramelteon
  • Theophylline Zileuton may increase the therapeutic and adverse effects of theophylline by increasing its serum concentration. Monitor for changes in the therapeutic and adverse effects of theophylline if zileuton is initiated, discontinued or dose changed. Dose alterations should be considered.
Liều Lượng & Cách Dùng : Tablet - Oral
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty : Cornerstone
    Sản phẩm biệt dược : Zyflo
  • Công ty : Cornerstone
    Sản phẩm biệt dược : Zyflo CR
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00744
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=60490
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46506394
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00414
ChemSpider
http://www.chemspider.com/Chemical-Structure.54531.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/68734-700-10
PharmGKB
http://www.pharmgkb.org/drug/PA451955
Wikipedia
http://en.wikipedia.org/wiki/Zileuton
RxList
http://www.rxlist.com/cgi/generic/zileuton.htm
Drugs.com
http://www.drugs.com/cdi/zileuton.html
... loading
... loading