Cyclohexylmethylpiperidinyltriphenylpropioamide: A Selective Muscarinic M 3 Antagonist Discriminating against the Other Receptor Subtypes

Tsukuba Research Institute, Edo, Tōkyō, Japan
Journal of Medicinal Chemistry (Impact Factor: 5.45). 03/2002; 45(4):984-7. DOI: 10.1021/jm010480k
Source: PubMed


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 M(3) 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).

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