Roflumilast N-oxide
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MedKoo CAT#: 329998

CAS#: 292135-78-5

Description: Roflumilast N-oxide is a phosphodiesterase 4 inhibitor. Roflumilast N-oxide is the active metabolite of roflumilast. Roflumilast N-Oxide in Combination with Formoterol Enhances the Antiinflammatory Effect of Dexamethasone in Airway Smooth Muscle Cells. Roflumilast n-oxide associated with PGE2 prevents the neutrophil elastase-induced production of chemokines by epithelial cells.


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Roflumilast N-oxide, purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 329998
Name: Roflumilast N-oxide
CAS#: 292135-78-5
Chemical Formula: C17H14Cl2F2N2O4
Exact Mass: 418.0299
Molecular Weight: 419.2058
Elemental Analysis: C, 48.71; H, 3.37; Cl, 16.91; F, 9.06; N, 6.68; O, 15.27


Synonym: Roflumilast N-oxide;

IUPAC/Chemical Name: N-(3,5-Dichloro-1-oxopyridin-4-yl)-4-difluoromethoxy-3-cyclopropylmethoxybenzamide

InChi Key: PCGSQNPMMSALEJ-UHFFFAOYSA-N

InChi Code: InChI=1S/C17H14Cl2F2N2O4/c18-11-6-23(25)7-12(19)15(11)22-16(24)10-3-4-13(27-17(20)21)14(5-10)26-8-9-1-2-9/h3-7,9,17H,1-2,8H2,(H,22,24)

SMILES Code: O=C(NC1=C(Cl)C=[N+]([O-])C=C1Cl)C2=CC=C(OC(F)F)C(OCC3CC3)=C2


Technical Data

Appearance:
Solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO

Shelf Life:
>2 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


References

1: Patel BS, Rahman MM, Baehring G, Xenaki D, Tang FS, Oliver BG, Ammit AJ. Roflumilast N-Oxide in Combination with Formoterol Enhances the Antiinflammatory Effect of Dexamethasone in Airway Smooth Muscle Cells. Am J Respir Cell Mol Biol. 2017 Apr;56(4):532-538. doi: 10.1165/rcmb.2016-0191OC. PubMed PMID: 27997807.

2: Li Q, Wang Y, Liu L, Ma P, Ding L. Pharmacokinetics of Roflumilast and Its Active Metabolite Roflumilast N-Oxide in Healthy Chinese Subjects After Single and Multiple Oral Doses. Eur J Drug Metab Pharmacokinet. 2017 Jun;42(3):371-381. doi: 10.1007/s13318-016-0343-4. PubMed PMID: 27306372.

3: Victoni T, Gicquel T, Bodin A, Daude M, Tenor H, Valença S, Devillier P, Porto LC, Lagente V, Boichot E. Roflumilast n-oxide associated with PGE2 prevents the neutrophil elastase-induced production of chemokines by epithelial cells. Int Immunopharmacol. 2016 Jan;30:1-8. doi: 10.1016/j.intimp.2015.11.019. Epub 2015 Nov 21. PubMed PMID: 26610096.

4: Milara J, Peiró T, Serrano A, Artigues E, Aparicio J, Tenor H, Sanz C, Cortijo J. Simvastatin Increases the Ability of Roflumilast N-oxide to Inhibit Cigarette Smoke-Induced Epithelial to Mesenchymal Transition in Well-differentiated Human Bronchial Epithelial Cells in vitro. COPD. 2015 Jun;12(3):320-31. doi: 10.3109/15412555.2014.948995. Epub 2014 Sep 10. PubMed PMID: 25207459.

5: Milara J, Lluch J, Almudever P, Freire J, Xiaozhong Q, Cortijo J. Roflumilast N-oxide reverses corticosteroid resistance in neutrophils from patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2014 Aug;134(2):314-22. doi: 10.1016/j.jaci.2014.02.001. Epub 2014 Mar 15. PubMed PMID: 24636089.

6: Milara J, Peiró T, Serrano A, Guijarro R, Zaragozá C, Tenor H, Cortijo J. Roflumilast N-oxide inhibits bronchial epithelial to mesenchymal transition induced by cigarette smoke in smokers with COPD. Pulm Pharmacol Ther. 2014 Aug;28(2):138-48. doi: 10.1016/j.pupt.2014.02.001. Epub 2014 Feb 11. PubMed PMID: 24525294.

7: Victoni T, Gleonnec F, Lanzetti M, Tenor H, Valença S, Porto LC, Lagente V, Boichot E. Roflumilast N-oxide prevents cytokine secretion induced by cigarette smoke combined with LPS through JAK/STAT and ERK1/2 inhibition in airway epithelial cells. PLoS One. 2014 Jan 8;9(1):e85243. doi: 10.1371/journal.pone.0085243. eCollection 2014. PubMed PMID: 24416369; PubMed Central PMCID: PMC3885699.

8: Vecchio D, Acquaviva A, Arezzini B, Tenor H, Martorana PA, Gardi C. Downregulation of NOX4 expression by roflumilast N-oxide reduces markers of fibrosis in lung fibroblasts. Mediators Inflamm. 2013;2013:745984. doi: 10.1155/2013/745984. Epub 2013 Aug 21. PubMed PMID: 24027357; PubMed Central PMCID: PMC3763264.

9: Thappali SR, Varanasi KV, Veeraraghavan S, Vakkalanka SK, Mukkanti K. Simultaneous quantitation of IC87114, roflumilast and its active metabolite roflumilast N-oxide in plasma by LC-MS/MS: application for a pharmacokinetic study. J Mass Spectrom. 2012 Dec;47(12):1612-9. doi: 10.1002/jms.3103. PubMed PMID: 23280750.

10: Höhne K, Schliessmann SJ, Kirschbaum A, Plönes T, Müller-Quernheim J, Tenor H, Zissel G. Roflumilast-N-oxide induces surfactant protein expression in human alveolar epithelial cells type II. PLoS One. 2012;7(7):e38369. doi: 10.1371/journal.pone.0038369. Epub 2012 Jul 16. PubMed PMID: 22815690; PubMed Central PMCID: PMC3398032.

11: Vollert S, Kaessner N, Heuser A, Hanauer G, Dieckmann A, Knaack D, Kley HP, Beume R, Weiss-Haljiti C. The glucose-lowering effects of the PDE4 inhibitors roflumilast and roflumilast-N-oxide in db/db mice. Diabetologia. 2012 Oct;55(10):2779-2788. doi: 10.1007/s00125-012-2632-z. Epub 2012 Jul 13. PubMed PMID: 22790061.

12: Knebel NG, Herzog R, Reutter F, Zech K. Sensitive quantification of roflumilast and roflumilast N-oxide in human plasma by LC-MS/MS employing parallel chromatography and electrospray ionisation. J Chromatogr B Analyt Technol Biomed Life Sci. 2012 Apr 15;893-894:82-91. doi: 10.1016/j.jchromb.2012.02.038. Epub 2012 Mar 3. PubMed PMID: 22425388.

13: Milara J, Armengot M, Bañuls P, Tenor H, Beume R, Artigues E, Cortijo J. Roflumilast N-oxide, a PDE4 inhibitor, improves cilia motility and ciliated human bronchial epithelial cells compromised by cigarette smoke in vitro. Br J Pharmacol. 2012 Aug;166(8):2243-62. doi: 10.1111/j.1476-5381.2012.01929.x. PubMed PMID: 22385203; PubMed Central PMCID: PMC3448891.

14: Lahu G, Hünnemeyer A, Diletti E, Elmlinger M, Ruth P, Zech K, McCracken N, Facius A. Population pharmacokinetic modelling of roflumilast and roflumilast N-oxide by total phosphodiesterase-4 inhibitory activity and development of a population pharmacodynamic-adverse event model. Clin Pharmacokinet. 2010 Sep;49(9):589-606. doi: 10.2165/11536600-000000000-00000. PubMed PMID: 20690782.

15: Lahu G, Nassr N, Herzog R, Elmlinger M, Ruth P, Hinder M, Huennemeyer A. Effect of steady-state enoxacin on single-dose pharmacokinetics of roflumilast and roflumilast N-oxide. J Clin Pharmacol. 2011 Apr;51(4):586-93. doi: 10.1177/0091270010370590. Epub 2010 May 13. PubMed PMID: 20466871.

16: Sabatini F, Petecchia L, Boero S, Silvestri M, Klar J, Tenor H, Beume R, Hatzelmann A, Rossi GA. A phosphodiesterase 4 inhibitor, roflumilast N-oxide, inhibits human lung fibroblast functions in vitro. Pulm Pharmacol Ther. 2010 Aug;23(4):283-91. doi: 10.1016/j.pupt.2010.02.004. Epub 2010 Mar 11. PubMed PMID: 20226872.

17: Nassr N, Huennemeyer A, Herzog R, von Richter O, Hermann R, Koch M, Duffy K, Zech K, Lahu G. Effects of rifampicin on the pharmacokinetics of roflumilast and roflumilast N-oxide in healthy subjects. Br J Clin Pharmacol. 2009 Oct;68(4):580-7. doi: 10.1111/j.1365-2125.2009.03478.x. PubMed PMID: 19843061; PubMed Central PMCID: PMC2780283.

18: Lahu G, Huennemeyer A, Herzog R, McCracken N, Hermann R, Elmlinger M, Zech K. Effect of repeated dose of erythromycin on the pharmacokinetics of roflumilast and roflumilast N-oxide. Int J Clin Pharmacol Ther. 2009 Apr;47(4):236-45. PubMed PMID: 19356389.

19: Lahu G, Huennemeyer A, von Richter O, Hermann R, Herzog R, McCracken N, Zech K. Effect of single and repeated doses of ketoconazole on the pharmacokinetics of roflumilast and roflumilast N-oxide. J Clin Pharmacol. 2008 Nov;48(11):1339-49. doi: 10.1177/0091270008321941. Epub 2008 Aug 29. PubMed PMID: 18757786.

20: von Richter O, Lahu G, Huennemeyer A, Herzog R, Zech K, Hermann R. Effect of fluvoxamine on the pharmacokinetics of roflumilast and roflumilast N-oxide. Clin Pharmacokinet. 2007;46(7):613-22. PubMed PMID: 17596106.