Acylhydrazones as M1/M3 selective muscarinic agonists

被引：10

作者：

Wu, ESC ^{[1
]}

Kover, A ^{[1
]}

Loch, JT ^{[1
]}

Rosenberg, LP ^{[1
]}

Semus, SF ^{[1
]}

Verhoest, PR ^{[1
]}

Gordon, JC ^{[1
]}

Machulskis, AC ^{[1
]}

McCreedy, SA ^{[1
]}

Zongrone, J ^{[1
]}

Blosser, JC ^{[1
]}

机构：

[1] ASTRA ARCUS USA,DEPT BIOL,ROCHESTER,NY 14602

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1996年 / 6卷 / 21期

关键词：

D O I：

10.1016/0960-894X(96)00471-4

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

To improve receptor binding affinity and to investigate functional selectivity of 2,8-dimethyl-1-oxa-8-azaspiro[4.5]decan-3-one acetylhydrazone 2 at muscarinic receptor subtypes, a series of acylhydrazones A was synthesized. The SAR indicates that the binding affinity in the pirenzepine assay (Mi) correlates well with lipophilicity. Intrinsic activity (30% of carbachol response) of agonists at M1 remains unchanged. Compounds with n = 0 and 6, where X = NHCO(CH2)(n)Me, did not inhibit cAMP formation in rat heart membrane (M2). Most of the compounds are more efficacious at the M3 receptor than at M1. The results suggest that the M1 and M3 receptors can better tolerate bulky and long chained substituents than the M2 receptor. Copyright (C) 1996 Elsevier Science Ltd

引用

页码：2525 / 2530

页数：6

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Semus, S
Verhoest, PR
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Blosser, JC
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