ISOCYTOSINE H2-RECEPTOR HISTAMINE-ANTAGONISTS .3. THE SYNTHESIS AND BIOLOGICAL-ACTIVITY OF LUPITIDINE (SK-AND-F-93479) AND RELATED-COMPOUNDS

被引：21

作者：

BROWN, TH

ARMITAGE, MA

BLAKEMORE, RC

BLURTON, P

DURANT, GJ

GANELLIN, CR

IFE, RJ

PARSONS, ME

RAWLINGS, DA

SLINGSBY, BP

机构：

[1] UNIV TOLEDO,COLL PHARM,DEPT MED & BIOL CHEM,TOLEDO,OH 43606

[2] UNIV LONDON UNIV COLL,DEPT CHEM,LONDON WC1H 0AJ,ENGLAND

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 1990年 / 25卷 / 03期

关键词：

2-amino-4-pyrimidones (isocytosines); furans; H[!sub]2[!/sub]-receptor antagonists; lupitidine (SK&F 93479); Mannich bases; thiophenes;

D O I：

10.1016/0223-5234(90)90204-G

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 2-[2-(5-dimethylaminomethyl-2-furanylmethylthio)ethylamino]-4-pyrimidones is described containing a variety of substituents in the 5-position of the pyrimidone (isocytosine) ring. Good H2-receptor histamine antagonist activity is retained over a range of basic and neutral, polar and non-polar substituents and the majority of compounds are selective for the H2-receptor. Modifications have also been made to the furan ring and N,N-dimethylaminomethyl substituent and structure-activity observations are discussed. Compound (16f), 2-[2-(5-dimethylaminomethyl-2-furanylmethylthio)ethylamino]-5-(6-methyl-3-pyridylmethyl)-4-pyrimidone (SK&F 93479, lupitidine), a compound which shows an extended duration of anti-secretory activity in animal models, was selected for clinical investigation. © 1990.

引用

页码：217 / 226

页数：10

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