Synthesis and Evaluation of N1-Alkylindole-3-Ylalkylammonium Compounds as Nicotinic Acetylcholine Receptor Ligands
Bioorganic & Medicinal Chemistry, 20 (12):
3719-3727 (2012)DOI: 10.1016/j.bmc.2012.04.050
Abstract
In this study thirty-three novel indole derivatives were designed and synthesized based on the structure of deformylflustrabromine B (1), a metabolite isolated from the marine bryozoan Flustra foliacea L. The syntheses were carried out using standard methodologies and in good yields. The molecules were tested for their affinities for the α4β2∗, α3β4∗, α7∗ and (α1)2β1γδ nicotinic acetylcholine receptor (nAChR) subtypes. Binding assays showed that, among these ligands, compound 7c exhibited the highest affinity with Ki=136.1, 93.9 and 862.4nM for the α4β2∗, α3β4∗, and α7∗ nAChRs subtypes, respectively. These results indicated that the indole core might be a useful scaffold for the development of new potent and selective nAChR ligands.