Design and synthesis of ether analogues as potent and selective M2 muscarinic receptor antagonists

被引：60

作者：

Wang, YG ^{[1
]}

Chackalamannil, S ^{[1
]}

Chang, W ^{[1
]}

Greenlee, W ^{[1
]}

Ruperto, V ^{[1
]}

Duffy, RA ^{[1
]}

McQuade, R ^{[1
]}

机构：

[1] Schering Plough Res Inst, Kenilworth, NJ 07033 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 07期

关键词：

D O I：

10.1016/S0960-894X(01)00100-7

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel, selective M-2 muscarinic antagonists, which replace the metabolically labile styrenyl moiety of the prototypical M-2 antagonist 1 with an ether linkage, were synthesized. A detailed SAR study in this class of compounds has yielded highly active compounds that showed M-2 K-i values of < 1.0 nM and > 100-fold selectivity against M-1, M-3, and M-5 receptors. (C) 2001 Elsevier Science Ltd. All rights reserved.

引用

页码：891 / 894

页数：4

共 12 条

[1] Potential role of muscarinic agonists in Alzheimer's disease [J].

Avery, EE ;

Baker, LD ;

Asthana, S .

DRUGS & AGING, 1997, 11 (06) :450-459

[2]

Doods Henri N., 1995, Drugs of the Future, V20, P157

[3]

DORJE F, 1991, J PHARMACOL EXP THER, V256, P727

[4] Pharmacologic treatment of cognition in Alzheimer's dementia [J].

Farlow, MR ;

Evans, RM .

NEUROLOGY, 1998, 51 (01) :S36-S44

[5]

MARCH J, 1985, ADV ORG CHEM, P20

[6]

OPDENVELDE W, 1976, J AM GERIATR SOC, V24, P12

[7] NEUROTRANSMITTER ENZYME ABNORMALITIES IN SENILE DEMENTIA - CHOLINE-ACETYLTRANSFERASE AND GLUTAMIC-ACID DECARBOXYLASE ACTIVITIES IN NECROPSY BRAIN-TISSUE [J].

PERRY, EK ;

GIBSON, PH ;

BLESSED, G ;

PERRY, RH ;

TOMLINSON, BE .

JOURNAL OF THE NEUROLOGICAL SCIENCES, 1977, 34 (02) :247-265

[8]

QUIRION R, 1995, J NEUROSCI, V15, P1455

[9] Identification of side chains on 1,2,5-thiadiazole-azacycles optimal for muscarinic m1 receptor activation. [J].

Sauerberg, P ;

Jeppesen, L ;

Olesen, PH ;

Sheardown, MJ ;

Fink-Jensen, A ;

Rasmussen, T ;

Rimvall, K ;

Shannon, HE ;

Bymaster, FP ;

DeLapp, NW ;

Calligaro, DO ;

Ward, JS ;

Whitesitt, CA ;

Thomsen, C .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (20) :2897-2902

[10]

SILVERMAN RB, 1992, ORGANIC CHEM DRUG DE, pCH7

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