title: Synthesis and evaluation of N(1)-alkylindole-3-ylalkylammonium compounds as nicotinic acetylcholine receptor ligands.
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)(2)β1γδ nicotinic acetylcholine receptor (nAChR) subtypes. Binding assays showed that, among these ligands, compound 7c exhibited the highest affinity with K(i)=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.
authors.affiliation: Facultad de Química, Pontificia Universidad Católica de Chile, Vicuña Mackenna 4860, Casilla 306, Correo 22, Santiago, Chile. eperezh@uc.cl
authors.forename: Edwin G
authors.initials: EG
authors.lastname: Pérez
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Cassels
authors.forename: Christoph
authors.initials: C
authors.lastname: Eibl
authors.forename: Daniela
authors.initials: D
authors.lastname: Gündisch
mesh_terms: D000818:Animals; D002013:Bryozoa / Q000737:chemistry; D002417:Cattle; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D015394:Molecular Structure; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D007211:Indoles; D008024:Ligands; D000644:Quaternary Ammonium Compounds; D011978:Receptors, Nicotinic