Enantiomeric N-methyl-4-piperidyl benzilates as muscarinic receptor ligands: Radioligand binding studies and docking studies to models of the three muscarinic receptors M1, M2 and M3.

Abstract

Benzilic ester derivatives with a basic moiety like N-methyl-4-piperidyl benzilates are potential drugs for the treatment of urinary incontinence, duodenal and gastric ulcers and Parkinson's disease. The effect of structural variations of chiral N-methyl-4-piperidyl benzilates was investigated using radioligand binding studies on muscarinic receptors (M1-M3). The results of the binding studies demonstrate that the absolute configuration and the aromatic substituent of benzilates have an influence on muscarinic affinity and selectivity. In this regard, (S)-configuration of benzilates and hydrophilic aromatic substituents seems to enhance muscarinic affinity. A model of the receptor ligand complex for N-methyl-4-piperidyl benzilates was obtained by molecular modelling. Both the affinity of enantiomeric benzilic esters and the subtype selectivity for muscarinic receptors are comprehensively explained by this model.

• Authors: Jana Selent, Wolfgang Brandt, Dirk Pamperin, Berthold Göber
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 14 Issue 6 Pg. 1729-36 (Mar 15 2006) ISSN: 0968-0896 [Print] England
• PMID: 16290166 (Publication Type: Journal Article)

Chemical References

• Benzilates
• Ligands
• Muscarinic Agonists
• Piperidines
• Receptor, Muscarinic M1
• Receptor, Muscarinic M2
• Receptor, Muscarinic M3
• Receptors, Muscarinic

Topics

• Animals
• Benzilates (chemistry, metabolism)
• Binding Sites
• Cell Line
• Computer Simulation
• Ligands
• Models, Chemical
• Models, Molecular
• Muscarinic Agonists (chemistry, metabolism)
• Piperidines (chemistry, metabolism)
• Radioligand Assay
• Receptor, Muscarinic M1 (chemistry)
• Receptor, Muscarinic M2 (chemistry)
• Receptor, Muscarinic M3 (chemistry)
• Receptors, Muscarinic (chemistry)
• Stereoisomerism