Synthesis and biological evaluation of 1,2,3,4-tetrahydroisoquinoline derivatives as potent and selective M2 muscarinic receptor antagonists

被引：0
|
作者：
Watanabe, T
Kinoyama, I
Takizawa, K
Hirano, S
Shibanuma, T
机构：
[1] Yamanouchi Pharmaceut Co Ltd, Inst Drug Discovery Res, Tsukuba, Ibaraki 3058585, Japan
[2] Yamanouchi Pharmaceut Co Ltd, Clin Dev Div, Tsukuba, Ibaraki 3058585, Japan
来源：
CHEMICAL & PHARMACEUTICAL BULLETIN | 1999年 / 47卷 / 05期
关键词：
1,2,3,4-tetrahydroisoquinoline derivative; M-2 muscarinic receptor; antagonism; M-2; selectivity; bradycardia;
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 1,2,3,4-tetrahydroisoquinoline derivatives containing the 5,11-dihydro-6H-pyridol[2,3-b][1,4]benzodiazepin-6-one skeleton were prepared and evaluated for their in vitro binding affinities to muscarinic receptors and for antagonism of bradycardia in vivo. Among them, compound 3f had the highest affinity for M-2 muscarinic receptors in the heart (pKi=9.1) with low affinity for M-3 muscarinic receptors in the submandibular gland. A structure-activity relationship (SAR) study suggested that the benzene ring fused piperidine and the alkyl linker chain length are crucially important for increased M-2 affinity.
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页码：672 / 677
页数：6
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