Synthesis and evaluation of novel 2-oxo-1,2-dihydro-3-quinolinecarboxamide derivatives as serotonin 5-HT4 receptor agonists

被引：0
|
作者：
Suzuki, M [1 ]
Ohuchi, Y [1 ]
Asanuma, H [1 ]
Kaneko, T [1 ]
Yokomori, S [1 ]
Ito, C [1 ]
Isobe, Y [1 ]
Muramatsu, M [1 ]
机构：
[1] Taisho Pharmaceut Co Ltd, Res Ctr, Omiya, Saitama 3308530, Japan
来源：
CHEMICAL & PHARMACEUTICAL BULLETIN | 2000年 / 48卷 / 12期
关键词：
quinolinecarboxamide; serotonin 5-HT4 receptor-stimulating activity; structure-activity relationship;
D O I：
暂无
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of N-azabicycloalkyl-1-alkyl-2-oxo-1,2-dihydro-3-quinolinecarboxamides were synthesized and tested for serotonin 5-HT4 receptor-stimulating effects in the regulation of electrically-evoked contraction in guinea pig muscle. Among them, N-azabicycloalkyl-1-isopropyl-2-oxo-1,2-dihydro-3-quinolinecarboxamide (8c, 9c, 10c, 11c, 12c) exhibited potent serotonin 5-HT4 receptor-stimulating activity. The most potent compound, N-(endo-8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-1-isopropyl-2-oxo-1,2-dihydro-3-quinolinecarboxamide (8c, ED50= 36.3 nM), was seven times as active as cisapride, while 8c had no affinity for 5-HT1A, 5-HT1D, D-2, muscarinic M-2 or muscarinic M-3 receptors even at 10 muM. Compound Sc stimulated digestive tract motility in conscious fed dogs (1.0 mg/kg p.o.).
引用
收藏
页码：2003 / 2008
页数：6
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