Cyclohexylmethylpiperidinyltriphenylpropioamide:: A selective muscarinic M3 antagonist discriminating against the other receptor subtypes

被引：10

作者：

Sagara, Y ^{[1
]}

Sagara, T ^{[1
]}

Mase, T ^{[1
]}

Kimura, T ^{[1
]}

Numazawa, T ^{[1
]}

Fujikawa, T ^{[1
]}

Noguchi, K ^{[1
]}

Ohtake, N ^{[1
]}

机构：

[1] Banyu Tsukuba Res Inst, Merck Res Labs, Tsukuba, Ibaraki 3002611, Japan

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2002年 / 45卷 / 04期

关键词：

D O I：

10.1021/jm010480k

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

To discover a highly selective M-3 antagonist, a combinatorial library was prepared. The library was designed to identify a novel structural class of M-3 antagonists by exploring the spatial arrangement of the pharmacophores in known M-3 antagonists. After the evaluation of 1000 library members, a potent M-3 antagonist, 14a (K-i = 0.31 nM), with novel structural features was identified. Compound 14a showed high selectivity for M3 receptors over the other muscarinic receptor subtypes (M-1/M-3 = 380-fold, M-2/M-3 = 98-fold, M-4/M-3 = 45-fold, M-5/M-3 = 120-fold).

引用

页码：984 / 987

页数：4

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