Cyclohexylmethylpiperidinyltriphenylpropioamide: a selective muscarinic M(3) antagonist discriminating against the other receptor subtypes.

Article Details

Citation

Copy to clipboard

Sagara Y, Sagara T, Mase T, Kimura T, Numazawa T, Fujikawa T, Noguchi K, Ohtake N

Cyclohexylmethylpiperidinyltriphenylpropioamide: a selective muscarinic M(3) antagonist discriminating against the other receptor subtypes.

J Med Chem. 2002 Feb 14;45(4):984-7.

PubMed ID

11831911 [ View in PubMed

]

Abstract

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).

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Darifenacin	Muscarinic acetylcholine receptor M1	Ki (nM)	5.5	N/A	N/A	Details
Darifenacin	Muscarinic acetylcholine receptor M2	Ki (nM)	47	N/A	N/A	Details
Darifenacin	Muscarinic acetylcholine receptor M3	Ki (nM)	0.84	N/A	N/A	Details
Darifenacin	Muscarinic acetylcholine receptor M4	Ki (nM)	8.6	N/A	N/A	Details
Darifenacin	Muscarinic acetylcholine receptor M5	Ki (nM)	2.3	N/A	N/A	Details