TITLE: ANALYSIS OF SYNTHETIC INTERMEDIATES AND PRODUCTS OF 1904 BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY.
ABSTRACT:
The method of High performance liquid chromatography will be used for the analysis of synthetic intermediates and products of 1904. High performance liquid chromatography is a technique in analytical chemistry used to separate, identify and quantify each component in a mixture. High performance liquid chromatography is the most suitable method of analysis. Precisions, specificity, limits of detection and limits of quantification will be determined.
KEYWORDS:
1904 synthetic intermediates and products, analysis, High performance liquid chromatography.
- INTRODUCTION:
1904, [IY-81149, 2 (((4-methoxy-3-methyl)-2-pyridinyl)-methylsulfinyl)-5-(1H-pyrrol-1-lyl) 1H-benzimidazole], it has a molecular formula of C19H18N4O2S and molecular weight of 366.439g/mol. 1904 is a potent inhibitor of the enzyme gastric proton pump H /K -ATPase in inhibiting gastric acid secretion, which includes gastric and duodenal ulcer, reflux oesophagitis and Zollinger Ellison syndrome. Unlike other proton pump inhibitors (PPIs), 1904 with a longer plasma half-life (about 3.6 hours) produces a greater and prolongs acid-suppressing effect, avoiding the occurrence of nocturnal acid break (NAB) during the PPIs therapy. Besides, a greater safety could be assured by at least two factors. One is the significant reduction of dosage and lower toxicity for 1904 comparing to omeprazole. And the other one is the low variability of the pharmacokinetics and pharmacodynamics of 1904 attributed to its metabolism independent of CYP2C19, which played the predominant role in metabolism of other PPIs.
Chemical structure of 1904.
1904 is a substituted benzimidazole prodrug with selective and irreversible proton pump inhibitor activity. It is available in the strengths of 5mg, 10mg, 20mg.
Preclinical research found that 1904 had a more prolonged half-life and higher suppression of gastric acid secretion in a dose-dependent manner, and similar safety compared with omeprazole. A comparative pharmacodynamic study on patients with gastroesophageal reflux disease reported that 1904, at a dose of 5 mg, provided gastric pH control comparable with the use of 20 mg omeprazole, and at doses of 10 and 20 mg it was found to have a more powerful and longer-lasting acid-suppressant effect than omeprazole at a dose 20 mg.
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