ISOCYTOSINE H2-RECEPTOR HISTAMINE-ANTAGONISTS .1. OXMETIDINE AND RELATED-COMPOUNDS
ISOCYTOSINE H2-RECEPTOR HISTAMINE-ANTAGONISTS .1. OXMETIDINE AND RELATED-COMPOUNDS
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DOI：
10.1016/0223-5234(88)90167-5
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发表时间：
1988-01-01
影响因子：
6.7
通讯作者：
WALKER, TF
中科院分区：
文献类型：
--
作者：
BROWN, TH;BLAKEMORE, RC;WALKER, TF
A series of 2-[2-(5-methyl-4-imidazolylmethylthio)ethylamino]-4-pyrimidones was prepared based on cimetidine 1. The model compound 4 has modest H2-antagonist activity as shown by its ability to antagonize histamine-stimulated tachycardia in guinea pig right atrium in vitro and inhibit histamine-stimulated gastric acid secretion in the lumen-perfused stomach of the anaesthetized rat. Investigation of the effect of substituents in the pyrimidone ring showed that suitable substitution at the 5-position gave compounds with greatly increased activity, whereas substituents at other positions in the ring were not favourable for activity. Some structure-activity and structure-toxicity correlations are discussed. Compound 32 (oxmetidine, SK and F 92994) which has the most favourable combination of properties, was selected for clinical investigation.
