Abstract
During drug synthesis, control of impurities is very important to get high-qualified drugs. A number of studies have devoted to synthesize the impurities and study the structures to support the method of purification. In this paper, we first synthesize one impurity in esomeprazole, rel-2-[[(3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-6-methoxy-1H-benzimidazole, with readily available raw materials, simple operation procedures and relatively mild reaction. Besides, we characterized its structure by MS, IR, 1H-NMR and HPLC analyses. The purity of target compound is as high as 99.58%, which can be used as the reference substance of the impurities of esomeprazole.
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References
And Ellervik U, Magnusson G (2010) A high yielding chemical synthesis of sialyl Lewis x tetrasaccharide and Lewis x trisaccharide; examples of regio- and stereodifferentiated glycosylations. J Org Chem. https://doi.org/10.1002/chin.199921210
Andersson T, Röhss K, Bredberg E, Hassan-Alin M (2001) Pharmacokinetics and pharmacodynamics of esomeprazole, the S-isomer of omeprazole. Clin Pharmacokinet 15:1563–1569. https://doi.org/10.1046/j.jcis1365-2036.2001.01087.x
Boekelheide VC, Linn WJ (1954) Rearrangements of N-oxides. a novel synthesis of pyridyl carbinols and aldehydes. J Am Chem Soc 76:1286–1291. https://doi.org/10.1021/ja01634a026
Cardile S, Romano C (2012) Clinical utility of esomeprazole for treatment of gastroesophageal reflux disease in pediatric and adolescent patients. Adolesc Health Med Ther 3:27–31. https://doi.org/10.2147/ahmy.s23193
Cheng HC, Wu CT, Chang WL, Cheng WC, Chen WY, Sheu BS (2014) Double oral esomeprazole after a 3-day intravenous esomeprazole infusion reduces recurrent peptic ulcer bleeding in high-risk patients: a randomised controlled study. Gut 63:1864–1872. https://doi.org/10.1136/gutjnl-2013-306531
Getter T, Zaks I, Barhum Y, Ben-Zur T, Böselt S, Gregoire S, Viskind O, Shani T, Gottlied H, Green O, Shubely M, Senderowitz H, Israelson A, Kwon I, Petri S, Offen D, Gruzman A (2015) A chemical chaperone-based drug candidate is effective in a mouse model of amyotrophic lateral sclerosis (ALS). ChemMedChem 10:850–861. https://doi.org/10.1002/cmdc.201500045
Manimaran T, Stahly GP (1993) Optical purification of profen drugs. Tetrahedron Asymmetry 4:1949–1954. https://doi.org/10.1016/s0957-4166(00)80436-x
Reddy PS (2013) Complexity in estimation of esomeprazole and its related impurities’ stability in various stress conditions in low-dose aspirin and esomeprazole magnesium capsules. Sci Pharm 81:475–492. https://doi.org/10.3797/scipharm.1212-13
Stawny M, Piekarski M, Marciniec B (2016) Analysis of drug impurities. Handbook of trace analysis. Springer, Cham. https://doi.org/10.1007/978-3-319-19614-5_8
Sugano K, Kinoshita Y, Miwa H, Takeuchi T (2012) Randomised clinical trial: esomeprazole for the prevention of nonsteroidal anti-inflammatory drug-related peptic ulcers in Japanese patients. Aliment Pharmacol Ther 36:115–125. https://doi.org/10.1111/j.jcis1365-2036.2012.05133.x
Sugimoto M, Furuta T (2012) Efficacy of esomeprazole in treating acid-related diseases in Japanese populations. Clin Exp Gastroenterol 5:49–59. https://doi.org/10.2147/ceg.s23926
Tang RS, Wu JC (2013) Managing peptic ulcer and gastroesophageal reflux disease in elderly Chinese patients—focus on esomeprazole. Clin Interv Aging 8:1433–1443. https://doi.org/10.2147/cia.s41350
Thitiphuree S, Talley NJ (2000) Esomeprazole, a new proton pump inhibitor: pharmacological characteristics and clinical efficacy. Int J Clin Pract 54:537. https://doi.org/10.2169/internalmedicine.39.864
Tonini M, Vigneri S, Savarino V, Scarpignato C (2001) Clinical pharmacology and safety profile of esomeprazole, the first enantiomerically pure proton pump inhibitor. Dig Liver Dis 33:600–606. https://doi.org/10.1016/s1590-8658(01)80115-8
Vakil NB, Shaker R, Johnson DA, Kovacs T, Baerg RD, Hwang CEA, D’Amico D, Hamelin B (2001) The new proton pump inhibitor esomeprazole is effective as a maintenance therapy in GERD patients with healed erosive oesophagitis: a 6-month, randomized, double-blind, placebo-controlled study of efficacy and safety. Aliment Pharmacol Ther 15:927–935. https://doi.org/10.1046/j.jcis1365-2036.2001.01024.x
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This work is supported by Natural Science Foundation of Shandong Province (ZR2016EMM13), Natural Science Foundation of Shandong Province (ZR2017LC005) and the Key Research and Development Program of Shandong Province of China (Major Science and Technology Innovation Project) (2018 CXGC1107).
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Liu, ZT., Meng, X., Fang, SM. et al. Synthesis and characterization of one impurity in esomeprazole, an antiulcerative drug. Chem. Pap. 74, 867–877 (2020). https://doi.org/10.1007/s11696-019-00918-3
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DOI: https://doi.org/10.1007/s11696-019-00918-3