Abstract
A series of 2-guanidino-4-pyridylthiazole derivatives were synthesized and evaluated for anti-aspirin-ulcer, gastric antisecretory, and histamine-H2-receptor-antagonist activities. Several compounds showed superior anti-aspirin-ulcer activity to that of clinically used H2-antagonists in the rat. Among them, 4-[6-(acetamidomethyl)pyridin-2-yl]-2-guanidinothiazole (8) demonstrated potent inhibitory activities against gastric lesions caused by two kinds of nonsteroidal antiinflammatory drugs, aspirin and indomethacin, respectively, in addition to strong antisecretory activity. Compound 8 possessed a preventable ability for the aspirin-induced reduction of the gastric mucosal blood flow at an intragastric administration of 32 mg/kg in the rat. On the other hand, famotidine (32 mg/kg) exhibited no significant effect and ranitidine (100 mg/kg) aggravated the blood flow in this system.
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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Anti-Ulcer Agents / therapeutic use
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Aspirin
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Blood Flow Velocity / drug effects
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Dogs
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Gastric Acid / metabolism
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Gastric Mucosa / blood supply
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Guanidines / chemical synthesis*
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Guanidines / pharmacology
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Guanidines / therapeutic use
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Guinea Pigs
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Histamine / pharmacology
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Histamine H2 Antagonists / chemical synthesis*
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Histamine H2 Antagonists / pharmacology
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Histamine H2 Antagonists / therapeutic use
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Indomethacin
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Male
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Molecular Structure
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Myocardial Contraction / drug effects
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Rabbits
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Rats
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Rats, Sprague-Dawley
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Stomach Ulcer / chemically induced
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Stomach Ulcer / prevention & control*
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Thiazoles / chemical synthesis*
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Thiazoles / pharmacology
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Thiazoles / therapeutic use
Substances
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Anti-Ulcer Agents
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Guanidines
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Histamine H2 Antagonists
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Thiazoles
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4-(6-(acetamidomethyl)pyridin-2-yl)-2-guanidinothiazole
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Histamine
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Aspirin
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Indomethacin