REVERSIBLE INHIBITORS OF THE GASTRIC (H+/K+)-ATPASE .2. 1-ARYLPYRROLO[3,2-C]QUINOLINES - EFFECT OF THE 4-SUBSTITUENT

被引：58

作者：

LEACH, CA

BROWN, TH

IFE, RJ

KEELING, DJ

LAING, SM

PARSONS, ME

PRICE, CA

WIGGALL, KJ

机构：

[1] SmithKline Beecham Pharmaceuticals R & D, Herts AL6 9AR, Frythe, Welwyn

[2] AB Hässle, S-431 83, Mölndal

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1992年 / 35卷 / 10期

关键词：

D O I：

10.1021/jm00088a021

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Further work on compounds 1 has identified the 4-position as a site where substantial modifications are tolerated, leading to analogues which are more potent and less toxic than those described previously. The best compound in the series is 13a (SK&F 96356), which is a potent inhibitor of gastric acid secretion in both the pentagastrin-stimulated rat and the histamine-stimulated dog. This compound shows reversible, K+-competitive binding to the enzyme. Because of its fluorescent properties, it is also proving useful in vitro as a probe of the structure and function of the (H+/K+)-ATPase.

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页码：1845 / 1852

页数：8

相关论文

共 14 条

[1] REVERSIBLE INHIBITORS OF THE GASTRIC (H+/K+)-ATPASE .1. 1-ARYL-4-METHYLPYRROLO[3,2-C]QUINOLINES AS CONFORMATIONALLY RESTRAINED ANALOGS OF 4-(ARYLAMINO)QUINOLINES [J].

BROWN, TH ;

IFE, RJ ;

KEELING, DJ ;

LAING, SM ;

LEACH, CA ;

PARSONS, ME ;

PRICE, CA ;

REAVILL, DR ;

WIGGALL, KJ .

JOURNAL OF MEDICINAL CHEMISTRY, 1990, 33 (02) :527-533

[2] THE SYNTHESIS OF DICTAMNINE AND GAMMA-FAGARINE [J].

GRUNDON, MF ;

MCCORKINDALE, NJ .

JOURNAL OF THE CHEMICAL SOCIETY, 1957, (MAY) :2177-2185

[3] THE PREPARATION OF A PYRROLO (3'-2'-3-4)QUINOLONE FROM (2-ETHOXYETHYL)MALONDIANILIDE [J].

GRUNDON, MF ;

MCCORKINDALE, NJ .

JOURNAL OF THE CHEMICAL SOCIETY, 1957, (AUG) :3448-3450

[4] THE SYNTHESIS OF FURANO(3',2'-3,4)QUINOLINES AND THE STRUCTURE OF DICTAMNIC ACID [J].

GRUNDON, MF ;

MCCORKINDALE, NJ ;

RODGER, MN .

JOURNAL OF THE CHEMICAL SOCIETY, 1955, :4284-4290

[5]

Hansch C., 1979, SUBSTITUENT CONSTANT

[6]

IFE RJ, 1990, ANNU REP MED CHEM, V25, P159

[7] ANTIULCER AGENTS .4. CONFORMATIONAL CONSIDERATIONS AND THE ANTIULCER ACTIVITY OF SUBSTITUTED IMIDAZO[1,2-A]PYRIDINES AND RELATED ANALOGS [J].

KAMINSKI, JJ ;

PUCHALSKI, C ;

SOLOMON, DM ;

RIZVI, RK ;

CONN, DJ ;

ELLIOTT, AJ ;

LOVEY, RG ;

GUZIK, H ;

CHIU, PJS ;

LONG, JF ;

MCPHAIL, AT .

JOURNAL OF MEDICINAL CHEMISTRY, 1989, 32 (08) :1686-1700

[8] METHOD FOR SYNTHESIS OF UNSATURATED CARBONYL-COMPOUNDS [J].

KSANDER, GM ;

MCMURRY, JE ;

JOHNSON, M .

JOURNAL OF ORGANIC CHEMISTRY, 1977, 42 (07) :1180-1185

[9] ANTIULCER AGENTS - 4-SUBSTITUTED 2-GUANIDINOTHIAZOLES - REVERSIBLE, COMPETITIVE, AND SELECTIVE INHIBITORS OF GASTRIC H+,K+-ATPASE [J].

LAMATTINA, JL ;

MCCARTHY, PA ;

REITER, LA ;

HOLT, WF ;

YEH, LA .

JOURNAL OF MEDICINAL CHEMISTRY, 1990, 33 (02) :543-552

[10] EFFECT OF OMEPRAZOLE - A GASTRIC PROTON PUMP INHIBITOR - ON PENTAGASTRIN STIMULATED ACID-SECRETION IN MAN [J].

LIND, T ;

CEDERBERG, C ;

EKENVED, G ;

HAGLUND, U ;

OLBE, L .

GUT, 1983, 24 (04) :270-276