Gamma-lactams--a novel scaffold for highly potent and selective alpha 7 nicotinic acetylcholine receptor agonists

Albert Enz; Dominik Feuerbach; Mathias U Frederiksen; Conrad Gentsch; Konstanze Hurth; Werner Müller; Joachim Nozulak; Bernard L Roy

doi:10.1016/j.bmcl.2009.01.073

Gamma-lactams--a novel scaffold for highly potent and selective alpha 7 nicotinic acetylcholine receptor agonists

Bioorg Med Chem Lett. 2009 Mar 1;19(5):1287-91. doi: 10.1016/j.bmcl.2009.01.073. Epub 2009 Feb 7.

Authors

Albert Enz¹, Dominik Feuerbach, Mathias U Frederiksen, Conrad Gentsch, Konstanze Hurth, Werner Müller, Joachim Nozulak, Bernard L Roy

Affiliation

¹ Novartis Institutes for Biomedical Research, Neuroscience Disease Area, 4002 Basel, Switzerland.

PMID: 19208472
DOI: 10.1016/j.bmcl.2009.01.073

Abstract

A novel class of alpha7 nicotinic acetylcholine receptor (nAChR) agonists has been discovered through high-throughput screening. The cis gamma-lactam scaffold has been optimized to reveal highly potent and selective alpha7 nAChR agonists with in vitro activity and selectivity and with good brain penetration in mice.

Publication types

Comparative Study

MeSH terms

Animals
Binding Sites
Brain / metabolism
Humans
Lactams / chemistry*
Mice
Nicotinic Agonists / chemistry
Nicotinic Agonists / metabolism*
Protein Binding
Rabbits
Receptors, Nicotinic / chemistry
Receptors, Nicotinic / metabolism*
alpha7 Nicotinic Acetylcholine Receptor

Substances

Chrna7 protein, human
Chrna7 protein, mouse
Lactams
Nicotinic Agonists
Receptors, Nicotinic
alpha7 Nicotinic Acetylcholine Receptor