Improving the oral efficacy of CNS drug candidates:: Discovery of highly orally efficacious piperidinyl piperidine M2 muscarinic receptor antagonists

被引：10

作者：

Wang, YG ^{[1
]}

Chackalamannil, S ^{[1
]}

Hu, ZY ^{[1
]}

Greenlee, WJ ^{[1
]}

Clader, J ^{[1
]}

Boyle, CD ^{[1
]}

Kaminski, JJ ^{[1
]}

Billard, W ^{[1
]}

Binch, H ^{[1
]}

Crosby, G ^{[1
]}

Ruperto, V ^{[1
]}

Duffy, RA ^{[1
]}

Cohen-Williams, M ^{[1
]}

Coffin, VL ^{[1
]}

Cox, KA ^{[1
]}

Grotz, DE ^{[1
]}

Lachowicz, JE ^{[1
]}

机构：

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

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2002年 / 45卷 / 25期

关键词：

D O I：

10.1021/jm0255163

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In search of a backup M-2 muscarinic receptor antagonist to the previously reported compound 1, we discovered compound (+)-14, which showed superior oral efficacy in animal models. The improvement of oral efficacy was achieved by modulating both the molecular weight and lipophilicity of the lead compounds.

引用

页码：5415 / 5418

页数：4

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