Collect. Czech. Chem. Commun. 2011, 76, 781-801
Published online 2011-06-08 11:32:06

Synthesis of antagonists of muscarinic (M3) receptors

Kenneth J. Broadleya, Robin H. Daviesb, Christine Escargueila, Alan T. L. Leec, Peter Pensona and Eric J. Thomasc,*

a The Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK
b Muscagen Limited, 10, North Road, Cardiff, CF10 3DFY, UK
c School of Chemistry, University of Manchester, M13 9PL, UK


Several α-hydroxyamides with (2,6-dialkoxyphenoxy)methyl substituents have been prepared and their activities as antagonists of the M3 muscarinic receptor in guinea pig ileum have been evaluated. N-{1-[(Phenyl)methyl]piperidin-4-yl}-2-{2-[(2,6-dimethoxyphenoxy)-methyl]phenyl}-2-hydroxypropanamide and N-(1-[{6-amino-4-[(1-propylpiperidin-4-yl)methyl]pyridin-2-yl}methyl]piperidin-4-yl)-2-cyclopentyl-2-hydroxy-2-phenylacetamide were the most potent compounds prepared, the micromolar potency of the latter indicating that it may be worth further investigation.

Keywords: Muscarinic receptors; Antagonists; Suzuki–Miyaura coupling; α-Hydroxyamides; Alcohols; Amides; Biological activity; Medicinal chemistry.

References: 20 live references.