201677-61-4 Usage
Uses
Used in Pharmaceutical Industry:
Sivelestat sodium is used as a therapeutic agent for the treatment of acute lung injury associated with systemic inflammatory response syndrome. It works by inhibiting the activity of neutrophil elastase, which is responsible for damaging lung parenchymal cells and the extracellular matrix, leading to alveolar capillary barrier disruption.
Used in Research Applications:
Sivelestat sodium is used as a research tool to study the role of neutrophil elastase in various inflammatory processes. It is employed to investigate the formation of neutrophil extracellular traps (NETs) and to examine the effects of neutrophil elastase inhibition on LPS-induced NF-κB nuclear translocation in isolated rat pulmonary microvascular endothelial cells (PMVECs).
Used in Clinical Trials:
Sivelestat sodium is used in clinical trials to evaluate its efficacy and safety in improving respiratory function and facilitating early removal of patients from mechanical ventilation in cases of acute lung injury.
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).
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
Check Digit Verification of cas no
The CAS Registry Mumber 201677-61-4 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 2,0,1,6,7 and 7 respectively; the second part has 2 digits, 6 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 201677-61:
(8*2)+(7*0)+(6*1)+(5*6)+(4*7)+(3*7)+(2*6)+(1*1)=114
114 % 10 = 4
So 201677-61-4 is a valid CAS Registry Number.
InChI:InChI=1/C20H22N2O7S.Na.4H2O/c1-20(2,3)19(26)29-13-8-10-14(11-9-13)30(27,28)22-16-7-5-4-6-15(16)18(25)21-12-17(23)24;;;;;/h4-11,22H,12H2,1-3H3,(H,21,25)(H,23,24);;4*1H2/q;+1;;;;/p-1
