Abstract
Acid-related diseases of the upper gastrointestinal tract, especially gastroesophageal reflux disease (GERD), remain a widespread problem worldwide. In this paper, we reported the design, synthesis, and preliminary gastric antisecretory activity evaluation of novel pyrimidine derivatives as acid pump antagonists. The gastric antisecretory activity assay results showed that all compounds displayed potent gastric antisecretory activity when gastric secretion was stimulated by histamine. The most potent compound 5g exhibited even similar gastric antisecretory activity compared with the control revaprazan, and the relative inhibition rate was 93.0%, which was worthy of further investigation.
Keywords:
acid pump antagonists; bioisosterism; gastric antisecretory activity; pyrimidine derivatives; synthesis.
© 2014 John Wiley & Sons A/S.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Benzimidazoles / chemical synthesis
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Benzimidazoles / chemistry
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Benzimidazoles / pharmacology
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Drug Design*
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Gastric Acid / metabolism
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Gastric Mucosa / drug effects
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Gastric Mucosa / metabolism
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Hydrogen-Ion Concentration
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Isoquinolines / chemical synthesis
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Isoquinolines / chemistry
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Isoquinolines / pharmacology
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Male
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Proton Pump Inhibitors / chemical synthesis*
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Proton Pump Inhibitors / chemistry
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Proton Pump Inhibitors / pharmacology
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Pyrimidines / chemical synthesis
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Pyrimidines / chemistry*
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Pyrimidines / pharmacology
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Pyrimidinones / pharmacology
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Rats
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Rats, Sprague-Dawley
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Structure-Activity Relationship
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Tetrahydroisoquinolines / pharmacology
Substances
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2-(2-(1H-benzo(d)imidazol-2-ylthio)pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline
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Benzimidazoles
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Isoquinolines
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Proton Pump Inhibitors
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Pyrimidines
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Pyrimidinones
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Tetrahydroisoquinolines
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YH 1885