Enhancement of pharmacokinetic properties and in vivo efficacy of benzylidene ketal M2 muscarinic receptor antagonists via benzamide modification

被引：10

作者：

Boyle, CD ^{[1
]}

Vice, SF ^{[1
]}

Campion, J ^{[1
]}

Chackalamannil, S ^{[1
]}

Lankin, CM ^{[1
]}

McCombie, SW ^{[1
]}

Billard, W ^{[1
]}

Binch, H ^{[1
]}

Crosby, G ^{[1
]}

Williams, MC ^{[1
]}

Coffin, VL ^{[1
]}

Cox, KA ^{[1
]}

Grotz, DE ^{[1
]}

Duffy, RA ^{[1
]}

Ruperto, V ^{[1
]}

Lachowicz, JE ^{[1
]}

机构：

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 23期

关键词：

D O I：

10.1016/S0960-894X(02)00742-4

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We previously reported the initial discovery of a novel class of stabilized benzylidene ketal M-2 receptor antagonists. This paper discusses new analogues consisting of benzamide modifications which not only improved M-2 receptor affinity and selectivity, but also enhanced the pharmacokinetic properties of the series. These changes led to the discovery of a highly potent and selective M-2 antagonist, which demonstrated in vivo efficacy and had good bioavailability in multiple species. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：3479 / 3482

页数：4

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