High affinity ligands for the alpha7 nicotinic receptor that show no cross-reactivity with the 5-HT3 receptor

S Richard Baker; John Boot; Michael Brunavs; David Dobson; Rachel Green; Lorna Hayhurst; Martine Keenan; Louise Wallace

doi:10.1016/j.bmcl.2005.07.070

High affinity ligands for the alpha7 nicotinic receptor that show no cross-reactivity with the 5-HT3 receptor

Bioorg Med Chem Lett. 2005 Nov 1;15(21):4727-30. doi: 10.1016/j.bmcl.2005.07.070.

Authors

S Richard Baker¹, John Boot, Michael Brunavs, David Dobson, Rachel Green, Lorna Hayhurst, Martine Keenan, Louise Wallace

Affiliation

¹ Eli Lilly and Company Ltd., Lilly Research Centre, Erl Wood Manor, Windlesham, Surrey, GU20 6PH, UK.

PMID: 16165358
DOI: 10.1016/j.bmcl.2005.07.070

Abstract

Potent and selective ligands of the alpha7 nicotinic acetylcholine receptor are required to understand the pharmacological effect of alpha7 activation. A common cross-reactivity occurs with serotonergic 5-HT3 receptors with which alpha7 receptors have a high sequence homology. We demonstrate that certain quinuclidine 3-biaryl carboxamides are high affinity alpha7 ligands with an excellent binding selectivity over 5-HT3 receptors.

MeSH terms

Amides / chemical synthesis*
Amides / chemistry
Cross Reactions
Drug Delivery Systems
Humans
Ligands
Protein Binding
Quinuclidines / chemical synthesis*
Quinuclidines / chemistry
Radioligand Assay
Receptors, Nicotinic / chemistry*
Receptors, Serotonin, 5-HT3 / chemistry*
Structure-Activity Relationship
alpha7 Nicotinic Acetylcholine Receptor

Substances

Amides
Chrna7 protein, human
Ligands
Quinuclidines
Receptors, Nicotinic
Receptors, Serotonin, 5-HT3
alpha7 Nicotinic Acetylcholine Receptor