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Sivelestat sodium

CAS No.
201677-61-4
Chemical Name:
Sivelestat sodium
Synonyms
Elaspol;Sivelestat sodium;Sivelestat(anhydrous);SIVELESTAT SODIUM HYDRATE;EI546 sodium tetrahydrate;ONO5046 sodium tetrahydrate;LY544349 sodium tetrahydrate;Sivelestat sodium Impurity A;SIVELESTAT SODIUM TETRAHYDRATE;Ono-EI-600 sodium tetrahydrate
CBNumber:
CB4679778
Molecular Formula:
C20H25N2NaO8S
Molecular Weight:
476.48
MDL Number:
MFCD01937969
MOL File:
201677-61-4.mol
MSDS File:
SDS
Last updated:2024-03-13 16:52:01

Sivelestat sodium Properties

storage temp. Sealed in dry,Room Temperature
solubility Soluble in DMSO (up to 20 mg/ml).
form White solid.
color White
Stability Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 2 months
CAS DataBase Reference 201677-61-4(CAS DataBase Reference)
FDA UNII 737RR8Y409

SAFETY

Risk and Safety Statements

Symbol(GHS)  GHS hazard pictograms
GHS07
Signal word  Warning
Hazard statements  H302-H315-H319-H335
Precautionary statements  P261-P305+P351+P338
HS Code  2935909099

Sivelestat sodium price More Price(29)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Cayman Chemical 17779 Sivelestat (sodium salt hydrate) ≥98% 201677-61-4 5mg $62 2024-03-01 Buy
Cayman Chemical 17779 Sivelestat (sodium salt hydrate) ≥98% 201677-61-4 10mg $109 2024-03-01 Buy
Cayman Chemical 17779 Sivelestat (sodium salt hydrate) ≥98% 201677-61-4 25mg $254 2024-03-01 Buy
Cayman Chemical 17779 Sivelestat (sodium salt hydrate) ≥98% 201677-61-4 50mg $448 2024-03-01 Buy
American Custom Chemicals Corporation API0008936 SIVELESTAT SODIUM HYDRATE 97.00% 201677-61-4 1G $2073.23 2021-12-16 Buy
Product number Packaging Price Buy
17779 5mg $62 Buy
17779 10mg $109 Buy
17779 25mg $254 Buy
17779 50mg $448 Buy
API0008936 1G $2073.23 Buy

Sivelestat sodium Chemical Properties,Uses,Production

Description

Sivelestat is an acyl enzyme inhibitor of neutrophil elastase, developed as an injectable formulation for the treatment of acute lung injury associated with systemic inflammatory response syndrome. A neutrophil predominant inflammation associated with excessive release of human neutrophil elastase (HNE) from azurophilic granules is capable of damaging both the lung parenchymal cells and the extracellular matrix allowing an alveolar capillary barrier disruption. Sivelestat is a sulfonanilide-containing pivaloyloxy benzene derivative prepared in a three step synthesis. This agent acts as a reversible and selective inhibitor of HNE with an lG.0 value of 0.044 PM. Sivelestat has exhibited potent protective effects against various causes of lung injuries in animal models. In an acid-induced acute lung injury model in conscious hamster, administration of sivelestat for 48 h following HCI instillation, dose-dependently reduced mortality and significantly improved the protein levels in bronchoalveolar lavage fluids and pulmonary artery pressure. In a similar study, the agent inhibited the endotoxin-induced acute lung dysfunctions (marked elevation of pulmonary vascular permeability, leukocyte migration, hemorrhage and parenchymal injury) in different animal species. Moreover, in a cardiopulmonary bypass model in dog, sivelestat ameliorated the respiratory index and interstitial-intra-alveolar edema. Sivelestat has a relatively poor bioavailability, due to an extensive first-pass metabolism and is easily hydrolyzed in vitro to an inactive metabolite. In two animal species, the half-life time was approximately 5-7 min. Clinical trials have shown that treatment with the agent improves respiratory function and facilitates early removal of patients from mechanical ventilation. However, in the last clinical study, conducted by Eli Lilly in patients with acute lung injury, no difference in mortality and safety was seen between sivelestat and placebo.

Description

Sivelestat is an inhibitor of neutrophil elastase (IC50 = 44 nM for the human enzyme). It is selective for neutrophil elastase over trypsin, thrombin, plasmin, kallikrein, chymotrypsin, and cathepsin G at 100 μM. Sivelestat inhibits the formation of neutrophil extracellular traps (NETs) induced by ionomycin (Item Nos. 10004974 | 11932) in isolated mouse neutrophils. It decreases LPS-induced NF-κB nuclear translocation in isolated rat pulmonary microvascular endothelial cells (PMVECs) at 50 mM. Sivelestat (10 mg/kg) reduces pulmonary edema, increases in the number of cells in the lung tissue positive for myeloperoxidase (MPO), a marker of neutrophil infiltration, and the severity of lung injury in a rat model of LPS-induced acute lung injury.

Originator

Ono Pharmaceutical (Japan)

Uses

Treatment of acute lung injury; acute respiratory distress syndrome (elastase inhibitor).

Definition

ChEBI: Sivelestat sodium hydrate is a N-acylglycine. It is functionally related to a N-benzoylglycine.

brand name

Elaspol

Synthesis

The synthesis of sivelestat (24) started with the amide formation between 2- nitrobenzoyl chloride (203) and glycine benzyl ester p-tolene sulfonic acid salt (204) in the presence of TEA to give amide 205 in 90% yield. Amide 205 was then reduced with iron power under acidic conditions to give corresponding amine 206 in 81% yield. Alternatively, the mixture of activated Raney nickel, nitro compound 205, acetic acid and 1,3- dimethyl-2-imidazolinone (DMI) under 25 atmospheric pressure of hydrogen at 40oC in an autoclave can give the same free amine 206 in 88% yield. Free amine 206 was treated with p-pivaloyloxybenzenesulfonyl chloride (207) in pyridine to yield sulfonamide 208 in 87% yield. Benzyl ester 208 was converted to its free carboxylic acid under hydrogenation, and the carboxylic acid was subsequently basified to give sivelestat sodium (24).

Synthesis_201677-61-4

References

1) Kawabata et al. (1991), ONO-5046, a novel inhibitor of human neutrophil elastase; Biochem. Biophys. Res. Commun., 177 814 2) Hagiwara et al. (2009), Neutrophil elastase inhibitor (sivelestat) reduces the levels of inflammatory mediators by inhibiting NFκB; Inflamm. Res., 58 198 3) Young et al. (2007), Role of neutrophil elastase in LTB4-induced neutrophil transmigration in vivo assessed with a specific inhibitor and neutrophil elastase deficient mice; Br. J. Phamracol., 151 628 4) Iwamoto et al. (2009), Protective effect of sivelestat sodium hydrate (ONO-5046) on ischemic spinal cord injury; Interact. Cardiovasc. Thorac. Surg., 8 606 5) Iwata et al. (2010), Effect of neutrophil elastase inhibitor (sivelestat sodium) in the treatment of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): a systemic review and meta-analysis; Intern. Med., 49 2423

Sivelestat sodium Preparation Products And Raw materials

Raw materials

Preparation Products

Global( 142)Suppliers
Supplier Tel Email Country ProdList Advantage
airuikechemical co., ltd.
+undefined86-15315557071 15315557071@163.com China 527 58
CONIER CHEM AND PHARMA LIMITED
+8618523575427 sales@conier.com China 47465 58
TargetMol Chemicals Inc.
+1-781-999-5354 +1-00000000000 marketing@targetmol.com United States 19892 58
ANHUI WITOP BIOTECH CO., LTD
+8615255079626 eric@witopchemical.com China 23556 58
Dayang Chem (Hangzhou) Co.,Ltd.
571-88938639 +8617705817739 info@dycnchem.com CHINA 52867 58
InvivoChem
+1-708-310-1919 +1-13798911105 sales@invivochem.cn United States 6393 58
Hebei Duling International Trade Co. LTD
+8618032673083 sales05@hbduling.cn China 15755 58
LEAP CHEM CO., LTD.
+86-852-30606658 market18@leapchem.com China 24738 58
Chemtour Biotech Co., Ltd
+8617327281506 market@chemtour.com China 1472 58
PT CHEM GROUP LIMITED
+86-85511178 +86-85511178 peter68@ptchemgroup.com China 35453 58

View Lastest Price from Sivelestat sodium manufacturers

Image Update time Product Price Min. Order Purity Supply Ability Manufacturer
Sivelestat sodium tetrahydrate pictures 2024-03-13 Sivelestat sodium tetrahydrate
201677-61-4
US $0.00-0.00 / g 1g 99.9% 20 tons airuikechemical co., ltd.
Sivelestat sodium pictures 2023-03-14 Sivelestat sodium
201677-61-4
US $25.00 / kg 1kg 99% 1000kg Hebei Duling International Trade Co. LTD
  • Sivelestat sodium pictures
  • Sivelestat sodium
    201677-61-4
  • US $25.00 / kg
  • 99%
  • Hebei Duling International Trade Co. LTD

Sivelestat sodium Spectrum

SIVELESTAT SODIUM HYDRATE SIVELESTAT SODIUM TETRAHYDRATE n-[2-[[[4-(2,2-dimethyl-1-oxopropoxy)phenyl]sulfonyl]amino]benzoyl]-(s)-glycine monosodium salt tetrahydrate Sivelestat sodium N-[2-[[[4-(2,2-dimethyl-1-oxopropoxy)phenyl]sulfonyl]amino]benzoyl]-Glycine monosodium salt tetrahydrate Sivelestat(anhydrous) Glycine, N-[2-[[[4-(2,2-diMethyl-1-oxopropoxy)phenyl]sulfonyl]aMino]benzoyl]-, MonosodiuM salt, tetrahydrate sodium,2-[[2-[[4-(2,2-dimethylpropanoyloxy)phenyl]sulfonylamino]benzoyl]amino]acetate,tetrahydrate Sivelestat sodium Impurity A EI546 sodium tetrahydrate LY544349 sodium tetrahydrate ONO5046 sodium tetrahydrate LY 544349;ONO-5046;LY-544349;LY544349 Sivelestat sodium hydrate (ONO-5046 sodium hydrate) Propanoic acid, 2,2-dimethyl-, 4-[[[2-[[(carboxymethyl)amino]carbonyl]phenyl]amino]sulfonyl]phenyl ester, sodium salt, hydrate (1:1:4) Elaspol Sodium 2-(2-(4-(pivaloyloxy)phenylsulfonamido)benzamido)acetate tetrahydrate Ono-EI-600 sodium tetrahydrate 201677-61-4 C20H21N2O7SNa4H2O C20H21N2NaO7S C20H21N2NaO7S4H2O C20H29N2NaO11S