Abstract
With the aim of applying mast cell-stabilizing agents as antiulcer agents, N-(1H-tetrazol-5-yl)-2-anilino-5-pyrimidinecarboxamides were synthesized, and initially evaluated pharmacologically for activity in the rat passive cutaneous anaphylaxis test by oral administration. The most active compound 6 was proved to inhibit potently the release of histamine from passively sensitized rat peritoneal mast cells in vitro. When compared with other mast cell-stabilizing agents and an antiulcer agent, compound 6 was found to show excellent gastric mucosal protection and gastric antisecretion activities. Furthermore, compound 6 revealed good activity against acidified aspirin ulcer in rats and water-immersion stress ulcer in rats.
MeSH terms
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Animals
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Anti-Ulcer Agents / chemical synthesis*
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Anti-Ulcer Agents / pharmacology
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Aspirin
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Cimetidine / pharmacology
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Cromolyn Sodium / pharmacology
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Ethanol
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Histamine H1 Antagonists / pharmacology
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Histamine Release / drug effects*
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Mast Cells / drug effects
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Mast Cells / metabolism*
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Passive Cutaneous Anaphylaxis / drug effects
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Peritoneal Cavity / cytology
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Pyrimidines / chemical synthesis*
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Pyrimidines / pharmacology
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Rats
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Stomach Ulcer / chemically induced
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Stomach Ulcer / drug therapy
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Tetrazoles / chemical synthesis*
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Tetrazoles / pharmacology
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ortho-Aminobenzoates / pharmacology
Substances
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Anti-Ulcer Agents
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Histamine H1 Antagonists
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Pyrimidines
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Tetrazoles
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ortho-Aminobenzoates
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Ethanol
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Cimetidine
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tranilast
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Cromolyn Sodium
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Aspirin