title: Indene-based frameworks targeting the 5-HT6 serotonin receptor: ring constraint in indenylsulfonamides using cyclic amines and structurally abbreviated counterparts.
abstract: Further studies in quest of 5-HT(6) serotonin receptor ligands led to the design and synthesis of a few selected examples of N-(inden-5-yl)sulfonamides with a ring-constrained aminoethyl side chain at the indene 3-position, some of which exhibited a high binding affinity, such as the pyrrolidine analogue 28 (K(i)=3nM). Moreover, the structurally abbreviated N-(inden-5-yl)sulfonamides showed K(i) values > or = 43 nM, which indicates that neither the N,N-aminoethyl nor the conformationally restricted aminoethyl side arm at the indene 3-position are required for binding. Selected compounds were then tested in a functional cAMP stimulation assay and found to act as 5-HT(6) antagonists, although with moderate potency at the micromolar level.
authors.affiliation: Laboratori de Química Orgànica, Departament de Farmacologia i Química Terapèutica, Facultat de Farmàcia, Universitat de Barcelona, Avda. Joan XXIII s/n, 08028 Barcelona, Spain. ealcalde@ub.edu
authors.forename: Ermitas
authors.initials: E
authors.lastname: Alcalde
authors.forename: Neus
authors.initials: N
authors.lastname: Mesquida
authors.forename: Sara
authors.initials: S
authors.lastname: López-Pérez
authors.forename: Jordi
authors.initials: J
authors.lastname: Frigola
authors.forename: Ramon
authors.initials: R
authors.lastname: Mercè
authors.forename: Jörg
authors.initials: J
authors.lastname: Holenz
authors.forename: Marta
authors.initials: M
authors.lastname: Pujol
authors.forename: Enrique
authors.initials: E
authors.lastname: Hernández
mesh_terms: D000588:Amines / Q000737:chemistry*; D002460:Cell Line; D000242:Cyclic AMP / Q000737:chemistry; D003500:Cyclization; D006801:Humans; D007192:Indenes / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011985:Receptors, Serotonin / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D013449:Sulfonamides / Q000737:chemistry*
chemical_list: D000588:Amines; D007192:Indenes; D011985:Receptors, Serotonin; D013449:Sulfonamides; C097216:serotonin 6 receptor; D000242:Cyclic AMP